(+/-)-4-tert-butyl-3-cyano-1-(4-ethynylphenyl)-2,6,7-trioxabi cyclo[2.2.2]octane: synthesis of a remarkably potent GABAA receptor antagonist.
(+/-)-4-tert-butyl-3-cyano-1-(4-ethynylphenyl)-2,6,7-trioxabi cyclo[2.2.2]octane: synthesis of a remarkably potent GABAA receptor antagonist.
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(异)-4-叔丁基-3-氰基-1-(4-乙炔基苯基)-2,6,7-三氧杂二环[2.2.2]辛烷：合成一种非常有效的GABAA受体拮抗剂。
DOI：
10.1021/jm00401a002
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发表时间：
1988
影响因子：
7.3
通讯作者：
Carida,JE
中科院分区：
文献类型：
--
作者：
Palmer,CJ;Cole,LM;Carida,JE
化学.如前所述制备化合物1。* 我们的2的合成（方案I）通过在氮气下在二氯甲烷中用氯铬酸吡啶鎓（1.5当量）氧化3-叔丁基-3-（羟甲基）氧杂环丁烷（3）8开始，得到3-叔丁基-3-甲酰基-氧杂环丁烷（4）（mp 120 ℃ dec），通过在Florisil上用乙醚进行色谱法以80%产率回收。用氰化钠（3.6当量）在水中在搅拌下在氮气下处理在醚中的新鲜制备的4和碘苯甲酰氯（1.4当量）过夜，得到（±）-3-叔丁基-3-[[（4-碘苯甲酰基）氧基]氰基甲基]氧杂环丁烷（5）（通过原位形成氧杂环丁烷氰醇），在用醚萃取时以90%收率回收。氧杂环丁烷酯5经刘易斯酸催化还原8，9生成（±）-4-叔丁基-3-氰基-1-（4-碘苯基）-2，6，7-三氧杂双环[2.2. 2]辛烷（6）通过在-70 ℃下在氮气下用三氟化硼醚合物（1.3当量）在无水二氯甲烷中处理来进行。6的回收率（58%）（mp 155-157 ℃）包括用三乙胺中和，在二氯甲烷和水之间分配，用己烷/二氯甲烷在碱性氧化铝上进行有机相的色谱分离。
Chemistry. Compound 1 was prepared as described earlier. 8 9* Our synthesis of 2 (Scheme I) was initiated by oxidation of 3-£ eri-butyl-3-(hydroxymethyl) oxetane (3) 8 with pyridinium chlorochromate (1.5 equiv) in dichloro-methane under nitrogen to give 3-£ erf-butyl-3-formyl-oxetane (4)(mp 120 C dec) recovered in 80% yield by chromatography on Florisil with ether. Treatment of freshly prepared 4 and iodobenzoyl chloride (1.4 equiv) in ether with sodium cyanide (3.6 equiv) in water with stirring overnight under nitrogen gave (±)-3-fer£-butyl-3-[[(4-iodobenzoyl) oxy] cyanomethyl] oxetane (5)(viain situ formation of the oxetane cyanohydrin) recovered in 90% yield on extraction with ether. Lewis acid catalyzed re-arrangement8, 9 of oxetane ester 5 to (±)-4-£ ert-butyl-3-cyano-l-(4-iodophenyl)-2, 6, 7-trioxabicyclo [2.2. 2] octane (6) was carried out by treatment with boron trifluoride etherate (1.3 equiv) in dry dichloromethane at-70 C under nitrogen. Recovery of 6 (58%)(mp 155-157 C) involved neutralization with triethylamine, partitioning between dichloromethane and water, and chromatography of the organic phase on basic alumina with hexane/dichloro-