{"id":10904,"date":"2016-08-18T07:16:43","date_gmt":"2016-08-17T23:16:43","guid":{"rendered":"\/\/www.gsbet888.com\/?p=10904"},"modified":"2019-08-02T18:54:06","modified_gmt":"2019-08-02T10:54:06","slug":"post-10904","status":"publish","type":"post","link":"\/\/www.gsbet888.com\/%e5%8c%96%e5%ad%a6%e6%9d%82%e8%ae%b0\/2016\/08\/post-10904.html","title":{"rendered":"\u6709\u673a\u53cd\u5e94\u540e\u5904\u7406\u7684\u4e00\u4e9b\u5c0fTips"},"content":{"rendered":"<p>\u6709\u673a\u5316\u5b66\u5b9e\u9a8c\u8ddf\u505a\u996d\u4e00\u6837\uff0c\u662f\u9700\u8981\u4e00\u70b9\u70b9\u6280\u5de7\u7684\uff0c\u6280\u5de7\u7684\u597d\u574f\u51b3\u5b9a\u4e86\u4ea7\u7387\u7b49\u7b49\u3002\u6700\u8fd1\u5c0f\u7f16\u4ecb\u7ecd\u4e86\u597d\u51e0\u7bc7\u5b9e\u9a8c\u5ba4\u7684\u4e00\u4e9b\u5173\u4e8e\u7845\u80f6\uff0c\u8fc7\u67f1\u5b50\u7b49\u7b49\u7684\u5c0f\u6280\u5de7\u3002\u8fd9\u4e00\u6b21\uff0c\u4e3b\u8981\u60f3\u5199\u4e00\u4e0b\u6709\u673a\u5408\u6210\u5b9e\u9a8c\u540e\u5904\u7406\u76f8\u5173\u768410\u4e2a\u5c0fTips\u3002\u5f53\u7136\uff0c\u66f4\u591a\u7684\u5c0f\u6280\u5de7\u9700\u8981\u5404\u4f4d\u8bfb\u8005\u7684\u8865\u5145\uff0c\u5b8c\u5584\u3002<\/p>\n<p><strong>1) \u4e09\u82ef\u57fa\u81a6\u6c27\u5316\u7269\u7684\u9664\u53bb<\/strong><br \/>\n<a href=\"\/\/www.gsbet888.com\/reactions\/2014\/01\/post-77.html\">Wittig \u53cd\u5e94<\/a>\u4e2d\u751f\u6210\u7684\u4e09\u82ef\u57fa\u81a6\u6c27\u5316\u7269\uff08TPPO\uff09\u7531\u4e8e\u5206\u79bb\u56f0\u96be\uff0c\u5b83\u7684\u540e\u5904\u7406\u9664\u53bb\u4e00\u76f4\u662f\u4e00\u4e2a\u6bd4\u8f83\u68d8\u624b\u7684\u95ee\u9898\u3002\u4f5c\u4e3a\u6539\u8fdb\u65b9\u6cd5\u7684\u8bdd\uff0c\u8fd1\u5e74\u6765\u5f00\u53d1\u51fa\u6765\u4e86\u4e00\u4e9b\u6c34\u6eb6\u6027\u7684TPP\u884d\u751f\u7269\uff0c\u4f46\u662f\u5bf9\u4e8elarge-scale\u7684\u8bdd\uff0c\u6210\u672c\u8fc7\u9ad8\u662f\u4e00\u4e2a\u4e0d\u53ef\u903e\u8d8a\u7684\u969c\u788d\u3002\u5728\u8fd9\u91cc\u5c0f\u7f16\u4ecb\u7ecd\u4e00\u4e0b\u81ea\u5df1\u4e86\u89e3\u7684\u4e00\u4e9b\u9664\u53bbTPPO\u7684\u65b9\u6cd5\u3002<\/p>\n<p><strong>\u65b9\u6cd5\u4e00<\/strong>\uff1a<\/p>\n<p>\u5982\u679c\u53cd\u5e94\u540e\u7684\u76ee\u6807\u4ea7\u7269\u6eb6\u89e3\u6027\u6bd4\u8f83\u597d\u7684\u8bdd\uff0c\u7528\u6b63\u5df1\u70f7\/\u4e59\u919a =\u00a04\/1\uff5e2\/1\u6eb6\u89e3\u540e\uff0c\u6790\u51fa\u4e09\u82ef\u57fa\u81a6\u6c27\u5316\u7269\uff0c\u8fc7\u6ee4\u9664\u53bb\u5373\u53ef\uff08\u4e59\u919a\u7684\u6bd4\u4f8b\u8d8a\u4f4e\u7684\u8bdd\u4e09\u82ef\u57fa\u81a6\u6c27\u5316\u7269\u7684\u9664\u53bb\u8d8a\u5e72\u51c0\uff09<\/p>\n<p><strong>\u65b9\u6cd5\u4e8c<\/strong>\uff1a<\/p>\n<p>\u901a\u8fc7\u4e0e\u6c2f\u5316\u9541\u5f62\u6210\u91d1\u5c5e\u87af\u5408\u7269\u540e\u6c89\u6dc0\u6790\u51fa\uff0c\u8fc7\u6ee4\u9664\u53bb\u3002\u5728\u8fd9\u91cc\u9700\u8981\u6ce8\u610f\u7684\u5730\u65b9\u662f\uff0c\u6c2f\u5316\u9541\u7684\u8868\u9762\u5fc5\u987b\u5f88\u5e72\u51c0\uff0c\u4e0d\u7136\u6bd4\u8f83\u96be\u4e0eTPPO\u5f62\u6210\u87af\u5408\u7269\u3002<\/p>\n<p>\u5177\u4f53\u7ec6\u8282\u8bf7\u53c2\u8003\u00a0&#8220;Development of a Scalable Synthesis of Oxadiazole Based S1P1 Receptor Agonists&#8221;<a href=\"http:\/\/dx.doi.org\/10.1021\/op300345v\" target=\"_blank\"><em>Org. Process Res. Dev.<\/em> <strong>2013<\/strong>, <em>17<\/em>, 666.<\/a><\/p>\n<p>&nbsp;<\/p>\n<p><strong>2) \u6709\u673a\u9521\u5316\u5408\u7269\u7684\u9664\u53bb<\/strong><br \/>\n<a href=\"\/\/www.gsbet888.com\/reactions\/2014\/01\/%E6%96%BD%E8%92%82%E5%8B%92%E5%8F%8D%E5%BA%94migita-kosugi-stille-cross-coupling.html\">Stille\u5076\u8054\u53cd\u5e94<\/a>\u6216\u81ea\u7531\u57fa\u8fd8\u539f\u7b49\u53cd\u5e94\u4e2d\u4ea7\u751f\u7684\u542b\u9521\u7684\u526f\u4ea7\u7269\uff0c\u7531\u4e8e\u5176\u6bd2\u6027\u7b49\u95ee\u9898\uff0c\u662f\u5fc5\u987b\u9664\u53bb\u7684\u3002\u4f46\u662f\u8be5\u5316\u5408\u7269\u5e38\u5e38\u5728\u7845\u80f6\u67f1\u4e0a\u5bb9\u6613\u62d6\u5c3e\uff0c\u6240\u4ee5\u8981\u5b8c\u5168\u9664\u53bb\u5e76\u4e0d\u90a3\u4e48\u5bb9\u6613\u3002\u5982\u679c\u76ee\u6807\u4ea7\u7269\u80fd\u6eb6\u4e8e\u4e59\u8148\u800c\u96be\u6eb6\u4e8e\u4e59\u919a\uff08\u6216\u6b63\u5df1\u70f7\uff09\u7684\u8bdd\uff0c\u7c97\u4ea7\u7269\u53ef\u4ee5\u7528\u4e59\u8148\u6eb6\u89e3\u540e\uff0c\u518d\u7528\u4e59\u919a\uff08\u6216\u8005\u6b63\u5df1\u70f7\uff09\u8403\u53d6\uff08\u6709\u673a\u9521\u5316\u5408\u7269\u6eb6\u4e8e\u4e59\u919a\u3001\u6b63\u5df1\u70f7\u76f8\uff09\u9664\u53bb\u3002\u53e6\u5916\u6709\u673a\u9521\u5316\u5408\u7269\u7684\u5206\u6db2\u8403\u53d6\u5e38\u5e38\u5bb9\u6613\u4e73\u5316\uff0c\u8fd9\u65f6\u5019\u52a0\u5165\u4e00\u70b9CaF\u53ef\u4ee5\u4f7f\u5f97\u5206\u5c42\u66f4\u660e\u663e\u3002<\/p>\n<p>\u800c\u6700\u8fd1\u5c0f\u7f16\u4e5f\u4ecb\u7ecd\u4e86\u53e6\u4e00\u79cd\u53ef\u80fd\u662f\u6700\u7b80\u4fbf\u7684\u65b9\u6cd5\uff0c\u76f4\u63a5\u8fc7\u67f1\u5b50\u5206\u79bb\u51fa\u53bb\uff0c\u8be6\u7ec6\u8bf7\u53c2\u7167 <a href=\"\/\/www.gsbet888.com\/%E5%8C%96%E5%AD%A6%E6%9D%82%E8%AE%B0\/2016\/08\/post-10700.html\">\u542b\u9521\u526f\u4ea7\u7269\u4e0e\u7684\u9664\u53bb\u65b9\u6cd5\uff1a\u78b3\u9178\u94be\/\u7845\u80f6<\/a><\/p>\n<p>&nbsp;<\/p>\n<p><strong>3) \u5421\u5576\u7684\u9664\u53bb<\/strong><br \/>\n\u5206\u6db2\u6cd5\uff1a\u7528\u7a00\u76d0\u9178\u6216\u786b\u9178\u94dc\u6c34\u6eb6\u6db2\u8403\u53d6\uff0c\u5421\u5576\u6210\u76d0\u540e\u8f6c\u79fb\u5230\u6c34\u76f8\u4e2d\u9664\u53bb\u3002\u6d53\u7f29\u6cd5\uff1a\u7528\u65cb\u84b8\u76f4\u63a5\u9664\u53bb\uff0c\u53ef\u4ee5\u9009\u62e9\u7528\u7532\u82ef\u5171\u6cb8\u3002<\/p>\n<p>&nbsp;<\/p>\n<p><strong>4) \u94dc\u76d0\u7684\u9664\u53bb<\/strong><br \/>\n\u5bf9\u4e8e\u542b\u6709\u5927\u91cf\u94dc\u76d0\u7684\u53cd\u5e94\u7684\u540e\u5904\u7406\uff0c\u5148\u52a0\u5165\u57df\u9971\u548c\u6c2f\u5316\u94f5\u6c34\u6eb6\u6db2(\u6216\u8005\u6c28\u6c34)\u731d\u706d\u540e\uff0c\u6405\u62cc\u6570\u5206\u949f\u540e\uff0c\u5206\u6db2\u8403\u53d6\uff0c\u518d\u7528\u9971\u548c\u6c2f\u5316\u94f5\u6c34\u6eb6\u6db2(\u6216\u8005\u6c28\u6c34)\u6d17\u51e0\u6b21\u540e\u6536\u96c6\u6709\u673a\u76f8\u5e72\u71e5\u5373\u53ef\u3002\u949b\u76d0\u4e5f\u80fd\u7528\u76f8\u540c\u65b9\u6cd5\u9664\u53bb\u3002<\/p>\n<p>&nbsp;<\/p>\n<p><strong>5) DMF\u7684\u9664\u53bb<\/strong><br \/>\nDMF \u7684\u9664\u53bb\u5e38\u5e38\u91c7\u7528\u4e24\u79cd\u624b\u6bb5\uff0c\u5206\u6db2\u9664\u53bb\u6216\u8005\u76f4\u63a5\u51cf\u538b\u52a0\u70ed\u62bd\u5e72\u3002\u7528\u5206\u6db2\u8403\u53d6\u9664\u53bb\u7684\u65b9\u6cd5\u65f6\u5019\uff0c\u76f8\u6bd4\u4e8e\u6709\u673a\u76f8\u7528\u5355\u7eaf\u7684\u4e59\u9178\u4e59\u916f\u6765\u8bf4\uff0c\u7528\u4e59\u9178\u4e59\u916f\/\u6b63\u5df1\u70f7\u6216\u8005\u4e59\u9178\u4e59\u916f\/\u7532\u82ef\u7684\u6df7\u5408\u6709\u673a\u6eb6\u5242\u66f4\u4f73\u3002\u5982\u679c\u4ea7\u7269\u662f\u56fa\u4f53\u4e14\u4e0d\u6eb6\u4e8e\u6c34\u7684\u8bdd\uff0c\u53ef\u4ee5\u5728\u53cd\u5e94\u6db2\u4e2d\u52a0\u5165\u5927\u91cf\u7684\u6c34\uff0c\u4f7f\u76ee\u6807\u4ea7\u7269\u6790\u51fa\u540e\u8fc7\u6ee4\u5f97\u5230\u7c97\u4ea7\u7269\u3002<\/p>\n<p>&nbsp;<\/p>\n<p><strong>6) \u76ee\u6807\u4ea7\u7269\u6eb6\u5728\u6c34\u91cc\u8403\u53d6\u4e0d\u51fa<\/strong><br \/>\n\u7528\u6c2f\u4eff(\u4e8c\u6c2f\u7532\u70f7)\/\u5f02\u4e19\u9187(\u7532\u9187)\uff1d10\/1\uff5e3\/1 \u3001\u6216\u8005 THF \u8403\u53d6\u3001\u6216\u8005\u76f4\u63a5\u628a\u6c34\u5c42\u65cb\u5e72\u3002\u3002\u3002<\/p>\n<p>&nbsp;<\/p>\n<p><strong>7) \u5206\u6db2\u65f6\u5019\u989c\u8272\u592a\u6d53\u754c\u9762\u770b\u4e0d\u6e05<\/strong><br \/>\n\u9047\u5230\u8fd9\u79cd\u60c5\u51b5\uff0c\u5c0f\u7f16\u7684\u7b2c\u4e00\u9009\u62e9\u662f\u7528\u624b\u7535\u7b52\u7167\u7167\u3002\u6709\u673a\u5c42\u4e0e\u6c34\u5c42\u5bf9\u5149\u7684\u900f\u8fc7\u6027\u662f\u4e0d\u540c\u7684\uff0c\u6240\u4ee5\u7528\u8fd9\u79cd\u65b9\u6cd5\u57fa\u672c\u53ef\u4ee5\u5206\u8fa8\u51fa\u4e24\u76f8\u7684\u6db2\u9762\u5728\u54ea\u91cc\u3002\u53e6\u5916\uff0c\u52a0\u51b0\u6216\u8005\u628a\u6838\u78c1\u5e3d\u6254\u8fdb\u53bb\uff0c\u53ef\u4ee5\u6d6e\u5728\u754c\u9762\u4e0a\uff0c\u4e5f\u53ef\u4ee5\u7528\u4e8e\u5206\u8fa8 (\u540e\u8005\u5f15\u7528\u4e8e\u00a0<a href=\"http:\/\/stoltz.caltech.edu\/tips\/index.html\" target=\"_blank\">Stoltz \u5b9e\u9a8c\u5ba4<\/a>) \u3002<\/p>\n<p>&nbsp;<\/p>\n<p><strong>8) LAH\u7684\u540e\u5904\u7406<\/strong><br \/>\nLAH\u7684\u540e\u5904\u7406\u662f\u5fc5\u987b\u5f97\u7262\u8bb0\u7684\uff0c\u5b83\u7684\u5904\u7406\u65b9\u6cd5\u7684\u597d\u574f\u5bf9\u4ea7\u7387\u7684\u5f71\u54cd\u975e\u5e38\u5927\u3002<\/p>\n<p>\u63a8\u8350\u7684\u5904\u7406\u65b9\u6cd5\u6709\u4ee5\u4e0b\u51e0\u79cd\uff08\u53c2\u8003\u7ef4\u57fa\u767e\u79d1\uff09<\/p>\n<ul>\n<li>\u5bf9\u4e8e\u4f7f\u7528X g\u7684\u53cd\u5e94\u6db2\uff0c\u6309\u7167\u987a\u5e8f\u4f9d\u6b21\u7f13\u6162\u6ef4\u5165X mL\u6c34\u3001X mL\u768415%\u6c22\u6c27\u5316\u94a0\u6c34\u6eb6\u6db2\u30013X mL\u7684\u6c34\uff0c\u7136\u540e\u518d\u5728\u5ba4\u6e29\u6405\u62cc\u6570\u5206\u949f\u76f4\u5230\u4ea7\u751f\u7070\u8272\u6c89\u6dc0\u3002\u7136\u540e\u7528\u7802\u82af\u6f0f\u6597\u8fc7\u6ee4\uff0c\u81f3\u5c11\u752850X mL\u7684\u6709\u673a\u6eb6\u5242\u6d17\uff0c\u6700\u540e\u6536\u96c6\u6eb6\u5242\u65cb\u8f6c\u5e72\u71e5\u3002<\/li>\n<li>\u52a0\u5165\u5927\u91cf\u786b\u9178\u94a0\u5341\u6c34\u5408\u7269\uff0c\u5176\u4e2d\u542b\u6709\u7684\u6c34\u5206\u7528\u4e8e\u5206\u89e3LAH\u3002\u7136\u540e\u52a0\u5165\u4e59\u9178\u4e59\u916f\u6405\u62cc\uff0c\u4e0d\u6eb6\u7269\u7528\u7802\u82af\u6f0f\u6597\u8fc7\u6ee4\uff0c\u6709\u673a\u6eb6\u5242\u65cb\u84b8\u9664\u53bb\u5373\u53ef\u3002<\/li>\n<li>\u57280<sup>o<\/sup>C\u52a0\u5165\u9971\u548c\u6c2f\u5316\u94f5\u6c34\u6eb6\u6db2\u731d\u706d\u53cd\u5e94\uff0c\u7136\u540e\u52a0\u5165\u4e09\u4e59\u80fa\/\u7532\u9187\/\u4e59\u9178\u4e59\u916f = 3:10:87\uff08\u53cd\u5e94\u6db2THF\u76842.5\u500d\u91cf\uff09\u6405\u62cc\uff0c\u7802\u82af\u8fc7\u6ee4\u540e\u8403\u53d6\uff0c\u5e72\u71e5\u3002<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p><strong>9) \u96f7\u5c3c\u954d\u7684\u540e\u5904\u7406<\/strong><br \/>\n\u96f7\u5c3c\u954d\u5177\u6709\u78c1\u6027\uff0c\u53ef\u4ee5\u5438\u9644\u5728\u5438\u94c1\u77f3\u4e0a\u3002\u6240\u4ee5\u53cd\u5e94\u7ed3\u675f\u540e\uff0c\u7528\u5438\u94c1\u77f3\u628a\u96f7\u5c3c\u954d\u5438\u5728\u74f6\u5b50\u5e95\u90e8\uff0c\u53cd\u5e94\u6db2\u76f4\u63a5\u8f6c\u79fb\u5230\u65b0\u7684\u74f6\u5b50\u4e2d\u5373\u53ef\uff0c\u5c31\u662f\u8fd9\u4e48\u4fbf\u5229\uff01<\/p>\n<p>&nbsp;<\/p>\n<p><strong>10) \u6c34\u94f6\u6ea2\u51fa\u7684\u5904\u7406\u65b9\u6cd5<\/strong><br \/>\n\u6c34\u94f6\u538b\u529b\u8ba1\u548c\u6c34\u94f6\u6e29\u5ea6\u8ba1\u4e0d\u5c0f\u5fc3\u6253\u788e\u540e~~\u3002\u8fd9\u65f6\u5019\u6ea2\u51fa\u7684\u6709\u6bd2\u6c34\u94f6\u600e\u4e48\u529e\uff1f\u5176\u5b9e\u5f88\u7b80\u5355\uff01\u76f4\u63a5\u6254\u5feb\u5e72\u51b0\uff0c\u628a\u6c34\u94f6\u51bb\u6210\u56fa\u4f53\u6536\u96c6\u6e05\u7406\u5c31\u884c\u3002<\/p>\n<p>&nbsp;<\/p>\n<p>\u8ffd\u52a0\uff1a<\/p>\n<p><strong>11) PCC\u6c27\u5316\u53cd\u5e94\u7684\u540e\u5904\u7406 \uff08\u70ed\u5fc3\u7f51\u53cb\u5305\u793c\u6e0a\u63d0\u4f9b\uff09<\/strong><\/p>\n<p>\u542b\u6709\u91cd\u91d1\u5c5e\u94ec\u7684\u6c27\u5316\u53cd\u5e94\u5b8c\u540e\uff0c\u5148\u7528\u7845\u85fb\u571f\u6216\u8005\u7845\u80f6\u8fc7\u6ee4\u4e0b\uff0c\u518d\u5904\u7406\u7684\u8bdd\uff0c\u53d7\u539f\u672c\u9ed1\u7cca\u7cca\u4f53\u7cfb\u5f71\u54cd\u5c31\u5c0f\u591a\u4e86\u3002<\/p>\n<p>&nbsp;<\/p>\n<p><strong>12) \u7898\u7f38\u6253\u7ffb\u540e \uff08\u70ed\u5fc3\u7f51\u53cbChirality\u63d0\u4f9b\uff09<\/strong><\/p>\n<p>\u7528\u786b\u4ee3\u786b\u9178\u94a0\u6eb6\u6db2\u6492\u5728\u6253\u7ffb\u7684\u7898\u4e0a\uff0c\u5c06\u7898\u5355\u8d28\u8fd8\u539f\u4e3a\u7898\u79bb\u5b50\uff0c\u9632\u6b62\u7898\u6325\u53d1\u3002(\u6211\u4eec\u5728\u505a\u6eb4\u4ee3\u53cd\u5e94\u65f6\u5019\u5904\u7406\u591a\u4f59\u7684\u6db2\u4f53\u6eb4\uff0c\u8403\u53d6\u65f6\u4e5f\u662f\u52a0\u5165\u786b\u4ee3\u786b\u9178\u94a0\u6c34\u6eb6\u6db2\u5904\u7406)<\/p>\n<p>&nbsp;<\/p>\n<p><strong>\u672c\u6587\u7248\u6743\u5c5e\u4e8e\u00a0<a href=\"\/\/www.gsbet888.com\/\">Chem-Station\u5316\u5b66\u7a7a\u95f4<\/a>\uff0c \u6b22\u8fce\u70b9\u51fb\u6309\u94ae\u5206\u4eab\uff0c\u672a\u7ecf\u8bb8\u53ef\uff0c\u8c22\u7edd\u8f6c\u8f7d\uff01<\/strong> <\/p>\n","protected":false},"excerpt":{"rendered":"\u6709\u673a\u5316\u5b66\u5b9e\u9a8c\u8ddf\u505a\u996d\u4e00\u6837\uff0c\u662f\u9700\u8981\u4e00\u70b9\u70b9\u6280\u5de7\u7684\uff0c\u6280\u5de7\u7684\u597d\u574f\u51b3\u5b9a\u4e86\u4ea7\u7387\u7b49\u7b49\u3002\u6700\u8fd1\u5c0f\u7f16\u4ecb\u7ecd\u4e86\u597d\u51e0\u7bc7\u5b9e\u9a8c\u5ba4\u7684\u4e00\u4e9b\u5173\u4e8e\u7845\u80f6\uff0c\u8fc7\u67f1\u5b50\u7b49\u7b49\u7684\u5c0f\u6280\u5de7\u3002\u8fd9\u4e00\u6b21\uff0c\u4e3b\u8981\u60f3\u5199\u4e00\u4e0b\u6709\u673a\u5408\u6210\u5b9e\u9a8c\u540e\u5904\u7406\u76f8\u5173\u768410\u4e2a\u5c0fTips\u3002\u5f53\u7136\uff0c\u66f4\u591a\u7684\u5c0f\u6280\u5de7\u9700\u8981\u5404\u4f4d\u8bfb\u8005\u7684\u8865\u5145\uff0c\u5b8c\u5584\u3002 1) \u4e09\u82ef\u57fa\u81a6\u6c27\u5316\u7269\u7684\u9664\u53bb Wittig \u53cd\u5e94\u4e2d\u751f\u6210\u7684\u4e09\u82ef\u57fa\u81a6\u6c27\u5316\u7269\uff08TPPO\uff09\u7531\u4e8e\u5206\u79bb\u56f0\u96be\uff0c\u5b83\u7684\u540e\u5904\u7406\u9664\u53bb\u4e00\u76f4\u662f\u4e00\u4e2a\u6bd4\u8f83\u68d8\u624b\u7684\u95ee\u9898\u3002\u4f5c\u4e3a\u6539\u8fdb\u65b9\u6cd5\u7684\u8bdd\uff0c\u8fd1\u5e74\u6765\u5f00\u53d1\u51fa\u6765\u4e86\u4e00\u4e9b\u6c34\u6eb6\u6027\u7684TPP\u884d\u751f\u7269\uff0c\u4f46\u662f\u5bf9\u4e8elarge-scale\u7684\u8bdd\uff0c\u6210\u672c\u8fc7\u9ad8\u662f\u4e00\u4e2a\u4e0d\u53ef\u903e\u8d8a\u7684\u969c\u788d\u3002\u5728\u8fd9\u91cc\u5c0f\u7f16\u4ecb\u7ecd\u4e00\u4e0b\u81ea\u5df1\u4e86\u89e3\u7684\u4e00\u4e9b\u9664\u53bbTPPO\u7684\u65b9\u6cd5\u3002 \u65b9\u6cd5\u4e00\uff1a \u5982\u679c\u53cd\u5e94\u540e\u7684\u76ee\u6807\u4ea7\u7269\u6eb6\u89e3\u6027\u6bd4\u8f83\u597d\u7684\u8bdd\uff0c\u7528\u6b63\u5df1\u70f7\/\u4e59\u919a =\u00a04\/1\uff5e2\/1\u6eb6\u89e3\u540e\uff0c\u6790\u51fa\u4e09\u82ef\u57fa\u81a6\u6c27\u5316\u7269\uff0c\u8fc7\u6ee4\u9664\u53bb\u5373\u53ef\uff08\u4e59\u919a\u7684\u6bd4\u4f8b\u8d8a\u4f4e\u7684\u8bdd\u4e09\u82ef\u57fa\u81a6\u6c27\u5316\u7269\u7684\u9664\u53bb\u8d8a\u5e72\u51c0\uff09 \u65b9\u6cd5\u4e8c\uff1a \u901a\u8fc7\u4e0e\u6c2f\u5316\u9541\u5f62\u6210\u91d1\u5c5e\u87af\u5408\u7269\u540e\u6c89\u6dc0\u6790\u51fa\uff0c\u8fc7\u6ee4\u9664\u53bb\u3002\u5728\u8fd9\u91cc\u9700\u8981\u6ce8\u610f\u7684\u5730\u65b9\u662f\uff0c\u6c2f\u5316\u9541\u7684\u8868\u9762\u5fc5\u987b\u5f88\u5e72\u51c0\uff0c\u4e0d\u7136\u6bd4\u8f83\u96be\u4e0eTPPO\u5f62\u6210\u87af\u5408\u7269\u3002 \u5177\u4f53\u7ec6\u8282\u8bf7\u53c2\u8003\u00a0&#8220;Development of a Scalable Synthesis of Oxadiazole Based S1P1 Receptor Agonists&#8221;Org. Process Res. Dev. 2013, 17, 666. &nbsp; 2) \u6709\u673a\u9521\u5316\u5408\u7269\u7684\u9664\u53bb Stille\u5076\u8054\u53cd\u5e94\u6216\u81ea\u7531\u57fa\u8fd8\u539f\u7b49\u53cd\u5e94\u4e2d\u4ea7\u751f\u7684\u542b\u9521\u7684\u526f\u4ea7\u7269\uff0c\u7531\u4e8e\u5176\u6bd2\u6027\u7b49\u95ee\u9898\uff0c\u662f\u5fc5\u987b\u9664\u53bb\u7684\u3002\u4f46\u662f\u8be5\u5316\u5408\u7269\u5e38\u5e38\u5728\u7845\u80f6\u67f1\u4e0a\u5bb9\u6613\u62d6\u5c3e\uff0c\u6240\u4ee5\u8981\u5b8c\u5168\u9664\u53bb\u5e76\u4e0d\u90a3\u4e48\u5bb9\u6613\u3002\u5982\u679c\u76ee\u6807\u4ea7\u7269\u80fd\u6eb6\u4e8e\u4e59\u8148\u800c\u96be\u6eb6\u4e8e\u4e59\u919a\uff08\u6216\u6b63\u5df1\u70f7\uff09\u7684\u8bdd\uff0c\u7c97\u4ea7\u7269\u53ef\u4ee5\u7528\u4e59\u8148\u6eb6\u89e3\u540e\uff0c\u518d\u7528\u4e59\u919a\uff08\u6216\u8005\u6b63\u5df1\u70f7\uff09\u8403\u53d6\uff08\u6709\u673a\u9521\u5316\u5408\u7269\u6eb6\u4e8e\u4e59\u919a\u3001\u6b63\u5df1\u70f7\u76f8\uff09\u9664\u53bb\u3002\u53e6\u5916\u6709\u673a\u9521\u5316\u5408\u7269\u7684\u5206\u6db2\u8403\u53d6\u5e38\u5e38\u5bb9\u6613\u4e73\u5316\uff0c\u8fd9\u65f6\u5019\u52a0\u5165\u4e00\u70b9CaF\u53ef\u4ee5\u4f7f\u5f97\u5206\u5c42\u66f4\u660e\u663e\u3002 \u800c\u6700\u8fd1\u5c0f\u7f16\u4e5f\u4ecb\u7ecd\u4e86\u53e6\u4e00\u79cd\u53ef\u80fd\u662f\u6700\u7b80\u4fbf\u7684\u65b9\u6cd5\uff0c\u76f4\u63a5\u8fc7\u67f1\u5b50\u5206\u79bb\u51fa\u53bb\uff0c\u8be6\u7ec6\u8bf7\u53c2\u7167 \u542b\u9521\u526f\u4ea7\u7269\u4e0e\u7684\u9664\u53bb\u65b9\u6cd5\uff1a\u78b3\u9178\u94be\/\u7845\u80f6 &nbsp; 3) \u5421\u5576\u7684\u9664\u53bb \u5206\u6db2\u6cd5\uff1a\u7528\u7a00\u76d0\u9178\u6216\u786b\u9178\u94dc\u6c34\u6eb6\u6db2\u8403\u53d6\uff0c\u5421\u5576\u6210\u76d0\u540e\u8f6c\u79fb\u5230\u6c34\u76f8\u4e2d\u9664\u53bb\u3002\u6d53\u7f29\u6cd5\uff1a\u7528\u65cb\u84b8\u76f4\u63a5\u9664\u53bb\uff0c\u53ef\u4ee5\u9009\u62e9\u7528\u7532\u82ef\u5171\u6cb8\u3002 &nbsp; 4) \u94dc\u76d0\u7684\u9664\u53bb \u5bf9\u4e8e\u542b\u6709\u5927\u91cf\u94dc\u76d0\u7684\u53cd\u5e94\u7684\u540e\u5904\u7406\uff0c\u5148\u52a0\u5165\u57df\u9971\u548c\u6c2f\u5316\u94f5\u6c34\u6eb6\u6db2(\u6216\u8005\u6c28\u6c34)\u731d\u706d\u540e\uff0c\u6405\u62cc\u6570\u5206\u949f\u540e\uff0c\u5206\u6db2\u8403\u53d6\uff0c\u518d\u7528\u9971\u548c\u6c2f\u5316\u94f5\u6c34\u6eb6\u6db2(\u6216\u8005\u6c28\u6c34)\u6d17\u51e0\u6b21\u540e\u6536\u96c6\u6709\u673a\u76f8\u5e72\u71e5\u5373\u53ef\u3002\u949b\u76d0\u4e5f\u80fd\u7528\u76f8\u540c\u65b9\u6cd5\u9664\u53bb\u3002 &nbsp; 5) DMF\u7684\u9664\u53bb DMF \u7684\u9664\u53bb\u5e38\u5e38\u91c7\u7528\u4e24\u79cd\u624b\u6bb5\uff0c\u5206\u6db2\u9664\u53bb\u6216\u8005\u76f4\u63a5\u51cf\u538b\u52a0\u70ed\u62bd\u5e72\u3002\u7528\u5206\u6db2\u8403\u53d6\u9664\u53bb\u7684\u65b9\u6cd5\u65f6\u5019\uff0c\u76f8\u6bd4\u4e8e\u6709\u673a\u76f8\u7528\u5355\u7eaf\u7684\u4e59\u9178\u4e59\u916f\u6765\u8bf4\uff0c\u7528\u4e59\u9178\u4e59\u916f\/\u6b63\u5df1\u70f7\u6216\u8005\u4e59\u9178\u4e59\u916f\/\u7532\u82ef\u7684\u6df7\u5408\u6709\u673a\u6eb6\u5242\u66f4\u4f73\u3002\u5982\u679c\u4ea7\u7269\u662f\u56fa\u4f53\u4e14\u4e0d\u6eb6\u4e8e\u6c34\u7684\u8bdd\uff0c\u53ef\u4ee5\u5728\u53cd\u5e94\u6db2\u4e2d\u52a0\u5165\u5927\u91cf\u7684\u6c34\uff0c\u4f7f\u76ee\u6807\u4ea7\u7269\u6790\u51fa\u540e\u8fc7\u6ee4\u5f97\u5230\u7c97\u4ea7\u7269\u3002 &nbsp; 6) \u76ee\u6807\u4ea7\u7269\u6eb6\u5728\u6c34\u91cc\u8403\u53d6\u4e0d\u51fa \u7528\u6c2f\u4eff(\u4e8c\u6c2f\u7532\u70f7)\/\u5f02\u4e19\u9187(\u7532\u9187)\uff1d10\/1\uff5e3\/1 \u3001\u6216\u8005 THF \u8403\u53d6\u3001\u6216\u8005\u76f4\u63a5\u628a\u6c34\u5c42\u65cb\u5e72\u3002\u3002\u3002 &nbsp; 7) \u5206\u6db2\u65f6\u5019\u989c\u8272\u592a\u6d53\u754c\u9762\u770b\u4e0d\u6e05 \u9047\u5230\u8fd9\u79cd\u60c5\u51b5\uff0c\u5c0f\u7f16\u7684\u7b2c\u4e00\u9009\u62e9\u662f\u7528\u624b\u7535\u7b52\u7167\u7167\u3002\u6709\u673a\u5c42\u4e0e\u6c34\u5c42\u5bf9\u5149\u7684\u900f\u8fc7\u6027\u662f\u4e0d\u540c\u7684\uff0c\u6240\u4ee5\u7528\u8fd9\u79cd\u65b9\u6cd5\u57fa\u672c\u53ef\u4ee5\u5206\u8fa8\u51fa\u4e24\u76f8\u7684\u6db2\u9762\u5728\u54ea\u91cc\u3002\u53e6\u5916\uff0c\u52a0\u51b0\u6216\u8005\u628a\u6838\u78c1\u5e3d\u6254\u8fdb\u53bb\uff0c\u53ef\u4ee5\u6d6e\u5728\u754c\u9762\u4e0a\uff0c\u4e5f\u53ef\u4ee5\u7528\u4e8e\u5206\u8fa8 (\u540e\u8005\u5f15\u7528\u4e8e\u00a0Stoltz \u5b9e\u9a8c\u5ba4) \u3002 &nbsp; 8) LAH\u7684\u540e\u5904\u7406 LAH\u7684\u540e\u5904\u7406\u662f\u5fc5\u987b\u5f97\u7262\u8bb0\u7684\uff0c\u5b83\u7684\u5904\u7406\u65b9\u6cd5\u7684\u597d\u574f\u5bf9\u4ea7\u7387\u7684\u5f71\u54cd\u975e\u5e38\u5927\u3002 \u63a8\u8350\u7684\u5904\u7406\u65b9\u6cd5\u6709\u4ee5\u4e0b\u51e0\u79cd\uff08\u53c2\u8003\u7ef4\u57fa\u767e\u79d1\uff09 \u5bf9\u4e8e\u4f7f\u7528X g\u7684\u53cd\u5e94\u6db2\uff0c\u6309\u7167\u987a\u5e8f\u4f9d\u6b21\u7f13\u6162\u6ef4\u5165X mL\u6c34\u3001X mL\u768415%\u6c22\u6c27\u5316\u94a0\u6c34\u6eb6\u6db2\u30013X mL\u7684\u6c34\uff0c\u7136\u540e\u518d\u5728\u5ba4\u6e29\u6405\u62cc\u6570\u5206\u949f\u76f4\u5230\u4ea7\u751f\u7070\u8272\u6c89\u6dc0\u3002\u7136\u540e\u7528\u7802\u82af\u6f0f\u6597\u8fc7\u6ee4\uff0c\u81f3\u5c11\u752850X mL\u7684\u6709\u673a\u6eb6\u5242\u6d17\uff0c\u6700\u540e\u6536\u96c6\u6eb6\u5242\u65cb\u8f6c\u5e72\u71e5\u3002 \u52a0\u5165\u5927\u91cf\u786b\u9178\u94a0\u5341\u6c34\u5408\u7269\uff0c\u5176\u4e2d\u542b\u6709\u7684\u6c34\u5206\u7528\u4e8e\u5206\u89e3LAH\u3002\u7136\u540e\u52a0\u5165\u4e59\u9178\u4e59\u916f\u6405\u62cc\uff0c\u4e0d\u6eb6\u7269\u7528\u7802\u82af\u6f0f\u6597\u8fc7\u6ee4\uff0c\u6709\u673a\u6eb6\u5242\u65cb\u84b8\u9664\u53bb\u5373\u53ef\u3002 \u57280oC\u52a0\u5165\u9971\u548c\u6c2f\u5316\u94f5\u6c34\u6eb6\u6db2\u731d\u706d\u53cd\u5e94\uff0c\u7136\u540e\u52a0\u5165\u4e09\u4e59\u80fa\/\u7532\u9187\/\u4e59\u9178\u4e59\u916f = 3:10:87\uff08\u53cd\u5e94\u6db2THF\u76842.5\u500d\u91cf\uff09\u6405\u62cc\uff0c\u7802\u82af\u8fc7\u6ee4\u540e\u8403\u53d6\uff0c\u5e72\u71e5\u3002 &nbsp; 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