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【结 构 式】

【分子编号】55741

【品名】ethyl 1-(2-{[2-(diethoxyphosphoryl)-2-fluoroacetyl][(1S)-1-phenylethyl]amino}acetyl)cyclopropanecarboxylate

【CA登记号】

【 分 子 式 】C22H31FNO7P

【 分 子 量 】471.4628452

【元素组成】C 56.05% H 6.63% F 4.03% N 2.97% O 23.75% P 6.57%

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:(VIII)

The intermediate fluoropyrrolidine (XIV) was obtained as follows: Alkylation of ethyl acetoacetate (I) with 1,2-dibromoethane (II) led to the cyclopropane derivative (III). Bromination of (III) provided bromo ketone (IV), which was condensed with (S)-1-phenylethylamine (V), yielding amino ketone (VI). Acylation of amine (VI) with (diethylfosfonyl)fluoroacetyl chloride (VII) gave amide (VIII). Intramolecular Wadsworth-Emmons condensation of keto phosphonate (VIII) in the presence of potassium tert-butoxide produced the pyrrolinone (IX). Catalytic hydrogenation of the pyrroline double bond of (IX), followed by separation of the resultant diastereomeric mixture, furnished pyrrolidinone (X). After saponification of the ethyl ester group of (X), the resulting acid (XI) was subjected to Curtius rearrangement in the presence of DPPA and t-BuOH, giving rise to carbamate (XII). Lactam (XII) reduction by means of borane in THF afforded pyrrolidine (XIII). The N-phenylethyl group of (XIII) was then removed by hydrogenation over Pd/C to furnish the required intermediate pyrrolidine (XIV) (See scheme no. 27170201a, intermediate (IX)).

1 Takahashi, H.; et al.; DQ-113 (D61-1113), a potent fluoroquinolone against multi-drug resistance Gram-positive bacteria: Practical synthesis, and in vitro and in vivo activities. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-550.
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) 11819 ethyl acetoacetate; ethyl 3-oxobutanoate;Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate 141-97-9 C6H10O3 详情 详情
(II) 10252 1,2-Dibromoethane; Ethylene dibromide 106-93-4 C2H4Br2 详情 详情
(III) 15171 ethyl 1-acetylcyclopropanecarboxylate C8H12O3 详情 详情
(IV) 15172 ethyl 1-(2-bromoacetyl)cyclopropanecarboxylate C8H11BrO3 详情 详情
(V) 20042 (1S)-1-phenyl-1-ethanamine; (1S)-1-phenylethylamine C8H11N 详情 详情
(VI) 55739 ethyl 1-(2-{[(1S)-1-phenylethyl]amino}acetyl)cyclopropanecarboxylate C16H21NO3 详情 详情
(VII) 55740 diethyl 2-chloro-1-fluoro-2-oxoethylphosphonate C6H11ClFO4P 详情 详情
(VIII) 55741 ethyl 1-(2-{[2-(diethoxyphosphoryl)-2-fluoroacetyl][(1S)-1-phenylethyl]amino}acetyl)cyclopropanecarboxylate C22H31FNO7P 详情 详情
(IX) 55742 ethyl 1-{4-fluoro-5-oxo-1-[(1S)-1-phenylethyl]-2,5-dihydro-1H-pyrrol-3-yl}cyclopropanecarboxylate C18H20FNO3 详情 详情
(X) 44225 ethyl 1-[(3S,4S)-4-fluoro-5-oxo-1-[(1S)-1-phenylethyl]pyrrolidinyl]cyclopropanecarboxylate C18H22FNO3 详情 详情
(XI) 55743 1-{(3S,4S)-4-fluoro-5-oxo-1-[(1S)-1-phenylethyl]pyrrolidinyl}cyclopropanecarboxylic acid C16H18FNO3 详情 详情
(XII) 55744 tert-butyl 1-{(3R,4S)-4-fluoro-5-oxo-1-[(1S)-1-phenylethyl]pyrrolidinyl}cyclopropylcarbamate C20H27FN2O3 详情 详情
(XIII) 55745 tert-butyl 1-{(3R,4S)-4-fluoro-1-[(1S)-1-phenylethyl]pyrrolidinyl}cyclopropylcarbamate C20H29FN2O2 详情 详情
(XIV) 44231 tert-butyl 1-[(3R,4S)-4-fluoropyrrolidinyl]cyclopropylcarbamate C12H21FN2O2 详情 详情
Extended Information