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【结 构 式】

【分子编号】31612

【品名】(2S)-2-[2-(tert-butoxy)-2-oxoethyl]-4-chloro-4-pentenoic acid

【CA登记号】

【 分 子 式 】C11H17ClO4

【 分 子 量 】248.70628

【元素组成】C 53.12% H 6.89% Cl 14.25% O 25.73%

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:(VII)

The condensation of dimethyl malonate (I) with 2-cloroallyl chloride (II) by means of sodium methoxide in hot methanol gives the alkylmalonate (III), which is treated with tert-butyl bromoacetate (IV), NaOH and benzyltriethylammonium chloride to yield the tricarboxylic ester (V). Partial decarboxylation of (V) with KOH in hot methanol/water affords the succinic acid derivative (VI), which is submitted to enzymatic hydrolysis with Alcalase 2.4L to provide the chiral monoester (VII). The condensation of monoacid (VII) with amine (VIII) by means of HOBT, DCC, and DIEA in THF gives the amide (IX), which is treated with TFA to eliminate the tert-butyl protecting group yielding the acid (X). The condensation of (X) with amine (XI) by means of NMM and pivaloyl chloride affords the amide (XII), which is treated with 2-methoxypropene (XIII) and TsOH in dichloromethane to protect the vicinal hydroxy groups giving the dioxolane (XIV). The bromination of the allyl double bond of (XIV) with NBS in tert-butyl methyl ether/water gives 3-bromo-2-oxopropyl derivative (XV).

1 Beaulieu, P.L.; et al.; Practical synthesis of BILA 2157 BS, a potent and orally active renin inhibitor: Use of an enzayme-catalyzed hydrolysis for the preparation of homochiral succinic acid derivatives. J Org Chem 1999, 64, 18, 6622.
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) 19373 dimethyl malonate;Methyl malonate;Propanedioic acid dimethyl ester 108-59-8 C5H8O4 详情 详情
(II) 31608 2,3-dichloro-1-propene 78-88-6 C3H4Cl2 详情 详情
(III) 31609 dimethyl 2-(2-chloro-2-propenyl)malonate C8H11ClO4 详情 详情
(IV) 17430 2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate 5292-43-3 C6H11BrO2 详情 详情
(V) 31610 1-(tert-butyl) 2,2-dimethyl 4-chloro-4-pentene-1,2,2-tricarboxylate C14H21ClO6 详情 详情
(VI) 31611 4-(tert-butyl) 1-methyl 2-(2-chloro-2-propenyl)succinate C12H19ClO4 详情 详情
(VII) 31612 (2S)-2-[2-(tert-butoxy)-2-oxoethyl]-4-chloro-4-pentenoic acid C11H17ClO4 详情 详情
(VIII) 29543 (2S,3R,4S)-2-amino-1-cyclohexyl-6-methyl-3,4-heptanediol C14H29NO2 详情 详情
(IX) 31613 tert-butyl (3S)-5-chloro-3-([[(1S,2R,3S)-1-(cyclohexylmethyl)-2,3-dihydroxy-5-methylhexyl]amino]carbonyl)-5-hexenoate C25H44ClNO5 详情 详情
(X) 31614 (3S)-5-chloro-3-([[(1S,2R,3S)-1-(cyclohexylmethyl)-2,3-dihydroxy-5-methylhexyl]amino]carbonyl)-5-hexenoic acid C21H36ClNO5 详情 详情
(XI) 29540 2-[(cyclohexylmethyl)amino]-N-methyl-N-[2-(2-pyridinyl)ethyl]acetamide C17H27N3O 详情 详情
(XII) 31615 (2S)-2-(2-chloro-2-propenyl)-N(4)-(cyclohexylmethyl)-N(1)-[(1S,2R,3S)-1-(cyclohexylmethyl)-2,3-dihydroxy-5-methylhexyl]-N(4)-(2-[methyl[2-(2-pyridinyl)ethyl]amino]-2-oxoethyl)butanediamide C38H61ClN4O5 详情 详情
(XIII) 17354 isopropenyl methyl ether; 2-methoxy-1-propene 116-11-0 C4H8O 详情 详情
(XIV) 31616 (2S)-2-(2-chloro-2-propenyl)-N(1)-[(1S)-2-cyclohexyl-1-[(4R,5S)-5-isobutyl-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl]-N(4)-(cyclohexylmethyl)-N(4)-(2-[methyl[2-(2-pyridinyl)ethyl]amino]-2-oxoethyl)butanediamide C41H65ClN4O5 详情 详情
(XV) 31617 (2R)-2-(3-bromo-2-oxopropyl)-N(1)-[(1S)-2-cyclohexyl-1-[(4R,5S)-5-isobutyl-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl]-N(4)-(cyclohexylmethyl)-N(4)-(2-[methyl[2-(2-pyridinyl)ethyl]amino]-2-oxoethyl)butanediamide C41H65BrN4O6 详情 详情
Extended Information