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【结 构 式】

【分子编号】14820

【品名】N-benzyl-2-chloro-N-phenylacetamide

【CA登记号】

【 分 子 式 】C15H14ClNO

【 分 子 量 】259.735

【元素组成】C 69.36% H 5.43% Cl 13.65% N 5.39% O 6.16%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(V)

The Wittig condensation of cis-bicyclo[4.3.0]nona-3-en-8-one (I) with triethyl phosphonoacetate (II) by means of NaH in THF gives 2-(cis-bicyclo[4.3.0]octa-3-en-8-ylidene)acetic acid ethyl ester (III), which is reduced with Li in liquid ammonia to the corresponding ethanol derivative (IV). The condensation of (IV) with N-benzyl-2-chloro-N-phenylacetamide (V) by means of NaH in toluene affords the corresponding ethoxyacetamide (VI), which is treated with ozone in methanol to give the epoxide (VII). Cleavage of (VII) with dimethyl sulfide in the same solvent yields the dialdehyde (VIII), which is submitted to an aldol cyclization by means of NaOH in methanol/water to afford the 2beta-formyl-3alpha-hydroxy derivative (IX). The Wittig condensation of aldehyde (IX) with dimethyl 4(S)-methyl-2-oxooctylphosphonate (X) by means of NaH in THF gives the unsaturated hydroxy ketone (XI). The ketone group of (XI) is reduced with NaBH4 in methanol, and the resulting diastereomeric diols obtained are separated by column chromatography to yield the alpha,alpha-dihydroxy compound (XII). The hydrolysis of (XII) with KOH in refluxing ethanol/water yields the corresponding free acid (XIII), which is finally methylated with diazomethane in ethyl ether to obtain a mixture of the epoxy alcohol (XXIVa) and the unsaturated alcohol (XXIVb). A chromatographic separation of the mixture followed by desilylation with acetic acid in methanol gives the desired final product.

1 Mealy, N.; Castaner, J.; Pimilprost. Drugs Fut 1996, 21, 4, 369.
2 Muraoka, M.; Nakamura, T.; Sugie, A.; Ono, K.; Yamamoto, M. (Sumitomo Pharmaceuticals Co., Ltd.); Bicyclooctane derivs. and their production and use. EP 0115954 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 14816 (3aR,7aS)-1,3,3a,4,7,7a-hexahydro-2H-inden-2-one C9H12O 详情 详情
(II) 10019 Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate 867-13-0 C8H17O5P 详情 详情
(III) 14818 ethyl 2-[(3aR,7aS)-1,3,3a,4,7,7a-hexahydro-2H-inden-2-ylidene]acetate C13H18O2 详情 详情
(IV) 14819 2-[(3aR,7aS)-2,3,3a,4,7,7a-hexahydro-1H-inden-2-yl]-1-ethanol C11H18O 详情 详情
(V) 14820 N-benzyl-2-chloro-N-phenylacetamide C15H14ClNO 详情 详情
(VI) 14821 2-[2-[(3aR,7aS)-2,3,3a,4,7,7a-hexahydro-1H-inden-2-yl]ethoxy]-N-benzyl-N-phenylacetamide C26H31NO2 详情 详情
(VII) 14822 2-[2-[(2aR,5aS)octahydro-1aH-indeno[5,6-b]oxiren-4-yl]ethoxy]-N-benzyl-N-phenylacetamide C26H31NO3 详情 详情
(VIII) 14823 N-benzyl-2-[2-[(3R,4S)-3,4-bis(2-oxoethyl)cyclopentyl]ethoxy]-N-phenylacetamide C26H31NO4 详情 详情
(IX) 14824 2-[2-[(2R,3aS,4R,5R,6aS)-4-formyl-5-hydroxyoctahydro-2-pentalenyl]ethoxy]-N-benzyl-N-phenylacetamide C26H31NO4 详情 详情
(X) 14825 dimethyl (4S)-4-methyl-2-oxooctylphosphonate C11H23O4P 详情 详情
(XI) 14826 2-(2-[(2R,3aS,4S,5R,6aS)-5-hydroxy-4-[(E,5S)-5-methyl-3-oxo-1-nonenyl]octahydro-2-pentalenyl]ethoxy)-N-benzyl-N-phenylacetamide C35H47NO4 详情 详情
(XII) 14827 2-(2-[(2R,3aS,4S,5R,6aS)-5-hydroxy-4-[(E,3S,5S)-3-hydroxy-5-methyl-1-nonenyl]octahydro-2-pentalenyl]ethoxy)-N-benzyl-N-phenylacetamide C35H49NO4 详情 详情
(XIII) 14828 2-(2-[(2R,3aS,4S,5R,6aS)-5-hydroxy-4-[(E,3S,5S)-3-hydroxy-5-methyl-1-nonenyl]octahydro-2-pentalenyl]ethoxy)acetic acid C22H38O5 详情 详情
Extended Information