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【结 构 式】

【分子编号】44096

【品名】ethyl (1R,2S,5S,6S)-2-hydroxy-4-oxobicyclo[3.1.0]hexane-6-carboxylate

【CA登记号】

【 分 子 式 】C9H12O4

【 分 子 量 】184.19188

【元素组成】C 58.69% H 6.57% O 34.75%

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)

Condensation of ethyl bromoacetate (I) with dimethyl sulfide gave the sulfonium salt (II). Addition of the sulfur ylide resulting from (II) and DBU to cyclopentenone (III) produced the bicyclic compound (IV). This was converted into the silyl enolate (V), which was subsequently oxidized to the unsaturated ketone (VI) by means of palladium diacetate. Alternatively, (IV) was directly oxidized to (VI) using allyl methyl carbonate and palladium diacetate. Treatment of enone (VI) with tert-butyl hydroperoxide and DBU produced epoxide (VII), which was further converted into hydroxy ketone (VIII) by reaction with diphenyl diselenide in the presence of N-acetyl-cysteine and sodium borate. Bucherer-Bergs reaction of ketone (VIII) with potassium cyanide and ammonium carbamate produced a mixture of diastereomeric hydantoins (IX). After N-alkylation of the hydantoin ring of (IX) with benzyl bromide, the desired isomer (X) was isolated by preparative HPLC. Finally, alcohol oxidation, with concomitant hydantoin hydrolysis, by treatment with Jones reagent furnished the title compound.

1 Massey, S.M.; Monn, J.A.; Valli, M.J. (Eli Lilly and Company); Excitatory amino acid receptor modulators. EP 0878463; US 5958960 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IXa) 44097   C11H14N2O5 详情 详情
(IXb) 44098   C11H14N2O5 详情 详情
(I) 16640 Ethyl 2-bromoacetate; Ethyl bromoacetate 105-36-2 C4H7BrO2 详情 详情
(II) 11947 (2-Ethoxy-2-oxoethyl)(dimethyl)sulfonium bromide 5187-82-6 C6H13BrO2S 详情 详情
(III) 25950 2-cyclopenten-1-one 930-30-3 C5H6O 详情 详情
(IV) 44092 ethyl (1S,5R,6S)-2-oxobicyclo[3.1.0]hexane-6-carboxylate C9H12O3 详情 详情
(V) 44093 ethyl (1S,5R,6S)-2-[(trimethylsilyl)oxy]bicyclo[3.1.0]hex-2-ene-6-carboxylate C12H20O3Si 详情 详情
(VI) 44094 ethyl (1R,5S,6S)-4-oxobicyclo[3.1.0]hex-2-ene-6-carboxylate C9H10O3 详情 详情
(VII) 44095 ethyl (1R,2R,4R,6S,7S)-5-oxo-3-oxatricyclo[4.1.0.0(2,4)]heptane-7-carboxylate C9H10O4 详情 详情
(VIII) 44096 ethyl (1R,2S,5S,6S)-2-hydroxy-4-oxobicyclo[3.1.0]hexane-6-carboxylate C9H12O4 详情 详情
(X) 44099   C18H20N2O5 详情 详情
Extended Information