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【结 构 式】

【分子编号】63959

【品名】(1S,2R)-2-fluoro-N-[(1R)-1-phenylethyl]cyclopropanecarboxamide

【CA登记号】

【 分 子 式 】C12H14FNO

【 分 子 量 】207.2477032

【元素组成】C 69.55% H 6.81% F 9.17% N 6.76% O 7.72%

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:(XIVb)

The chiral intermediate (1R,2S)-N-(tert-butoxycarbonyl)-2-fluorocyclopropylamine (III) is obtained as follows: 1) The cyclization of butadiene (IX) with dibromofluoromethane by means of BuONa, followed by oxidation with KMnO4, esterification with ethanol - sulfuric acid and reduction with tributyltin hydride gives 2-fluorocyclopropanecarboxylic acid ethyl ester as a cis/trans mixture (X), which is separated by crystallization. The cis-racemic-isomer (XI) is hydrolyzed with NaOH to the corresponding acid (XII), which is condensed with (R)-alpha-methylbenzylamine (XIII) by means of diphenyl chlorophosphate to give the mixture of diastereomers (XIV). This mixture is separated by crystallization, yielding pure (1S,2S)-2-fluoro-N-[alpha(R)-methylbenzyl]cyclopropanecarboxamide (XV), which is hydrolyzed with HCl to the corresponding free acid (XVI). Finally, this compound is converted into (III) by treatment with diphenylphosphoryl azide in refluxing tert-butanol.

1 Hayakawa, I.; Kimura, Y. (Daiichi Pharmaceutical Co., Ltd.); Optically active pyridone carboxylic acid derivs. AU 8933702; EP 0341493; JP 1990231475; JP 1995300416; JP 1999124367; JP 1999124380; US 5587386; US 5767127 .
2 Castaner, J.; Graul, A.; Prous, J.; DU-6859. Drugs Fut 1994, 19, 9, 827.
3 Sato, K.; Saito, T.; Hayakawa, I.; Sato, M.; Yafune, T.; Atarashi, S.; Une, T.; Kimura, Y.; Kawakami, K.; Design and structure-activity relationship of new N1-cis-2-fluorocyclopropyl quinolones. 31st. 31st Intersci Conf Antimicrob Agents Chemother (Sept 29-Oct 2, Chicago) 1991, Abst 1504.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XIVa) 15139 (1S,2S)-2-fluoro-N-[(1R)-1-phenylethyl]cyclopropanecarboxamide C12H14FNO 详情 详情
(XIVb) 63959 (1S,2R)-2-fluoro-N-[(1R)-1-phenylethyl]cyclopropanecarboxamide C12H14FNO 详情 详情
(III) 15127 tert-butyl N-[(1R,2S)-2-fluorocyclopropyl]carbamate 127199-16-0 C8H14FNO2 详情 详情
(IX) 11579 1,3-Butadiene; Butadiene 106-99-0 C4H6 详情 详情
(X) 15134 ethyl 2-fluorocyclopropanecarboxylate C6H9FO2 详情 详情
(XI) 63960 cis-rac[ethyl (1S,2S)-2-fluorocyclopropanecarboxylate] C6H9FO2 详情 详情
(XII) 63958 cis-rac(1S,2S)-2-fluorocyclopropanecarboxylic acid C4H5FO2 详情 详情
(XIII) 10039 (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine 3886-69-9 C8H11N 详情 详情
(XV) 15139 (1S,2S)-2-fluoro-N-[(1R)-1-phenylethyl]cyclopropanecarboxamide C12H14FNO 详情 详情
(XVI) 15140 (1S,2S)-2-fluorocyclopropanecarboxylic acid C4H5FO2 详情 详情
Extended Information