【结 构 式】 |
【分子编号】54950 【品名】5-oxo-3-phenyl-3-cyclohexene-1-carboxylic acid 【CA登记号】 |
【 分 子 式 】C13H12O3 【 分 子 量 】216.23648 【元素组成】C 72.21% H 5.59% O 22.2% |
合成路线1
该中间体在本合成路线中的序号:(XXI)A further procedure employed the chiral keto acid (XXII) as the key intermediate. The cyclohexenone carboxylic acid (XXI) was synthesized via aldol condensation between 3-benzoylacrylic acid (XIX) and ethyl acetoacetate (XX), followed by cyclization and decarboxylation under Robinson annulation reaction conditions. Resolution of (XXI) to furnish the desired (S)-enantiomer (XXII) was accomplished either via formation of the diastereomeric salts with cinchonidine or, alternatively, by esterification of (XXI) with n-butanol --yielding the isomeric mixture (XXIII)--, followed by enantioselective hydrolysis of the (S)-butyl ester from in the presence of alpha-chymotrypsin. Coupling of keto acid (XXII) with tetrahydropyridine (V) provided keto amide (XXIV). The keto group of (XXIV) was then reduced with NaBH4 to form a diastereomeric mixture of allylic alcohols (XXV), which were further reduced employing NaBH3CN in the presence of ZnCl2 to furnish the target (R)-cyclohexenecarboxamide (XXVI). The amide function of (XXVI) was finally reduced to the title amine by means of LiAlH4 in methyl tert-butyl ether.
【1】 Butler, D.E.; Wustrow, D.J.; Smith, W.J. III; Gailey, J. (Pfizer Inc.); Improved process for R (+) 1,2,3,6-tetrahydro-4-phenyl-1-[(3-phenyl-3-cyclohexen-1-yl)methyl]pyridine, a central nervous system agent. WO 9608473 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(V) | 13002 | 4-Phenyl-1,2,3,6-tetrahydropyridine; 1,2,3,6-Tetrahydro-4-phenyl-pyridine | 10338-69-9 | C11H13N | 详情 | 详情 |
(XIX) | 28661 | (E)-4-oxo-4-phenyl-2-butenoic acid | 583-06-2 | C10H8O3 | 详情 | 详情 |
(XX) | 11819 | ethyl acetoacetate; ethyl 3-oxobutanoate;Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate | 141-97-9 | C6H10O3 | 详情 | 详情 |
(XXI) | 54950 | 5-oxo-3-phenyl-3-cyclohexene-1-carboxylic acid | C13H12O3 | 详情 | 详情 | |
(XXII) | 54952 | (1S)-5-oxo-3-phenyl-3-cyclohexene-1-carboxylic acid | C13H12O3 | 详情 | 详情 | |
(XXIII) | 54951 | butyl 5-oxo-3-phenyl-3-cyclohexene-1-carboxylate | C17H20O3 | 详情 | 详情 | |
(XXIV) | 54953 | (5S)-3-phenyl-5-{[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]carbonyl}-2-cyclohexen-1-one | C24H23NO2 | 详情 | 详情 | |
(XXV) | 54954 | [(1S)-5-hydroxy-3-phenyl-3-cyclohexen-1-yl][4-phenyl-3,6-dihydro-1(2H)-pyridinyl]methanone | C24H25NO2 | 详情 | 详情 | |
(XXVI) | 50955 | 2-[7-fluoro-4-(2-hydroxyethyl)-2-oxo-1(2H)-quinolinyl]acetamide | C13H13FN2O3 | 详情 | 详情 |