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【结 构 式】

【分子编号】64494

【品名】6-phenyl-2,5-piperidinedione

【CA登记号】

【 分 子 式 】C11H11NO2

【 分 子 量 】189.21388

【元素组成】C 69.83% H 5.86% N 7.4% O 16.91%

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:(IV)

The cyclization of benzaldehyde (I) with methyl 4-nitrobutyrate (II) and ammonium acetate in refluxing acetic acid gives 5-nitro-6-phenylpiperidone (III), which is treated with ozone and t-BuOK in dichloromethane/methanol to yield 2-phenylpiperidine-3,6-dione (IV). The reduction of (IV) by means of LiAlH4 in THF affords 2-phenylpiperidin-3-ol (V) as a mixture of cis- and trans-isomers. The reaction of (V) with TsOH, followed by crystallization in methanol/ethyl acetate provides the corresponding tosylate (VI) as the (rac)(cis)-isomer. The neutralization of the tosylate (VI) with Na2CO3 in ethyl acetate/water gives 2-phenylpiperidin-3-ol (VII) as a racemic cis mixture, which is submitted to optical resolution with (+)-dibenzoyltartaric acid to yield (+)(cis)-(VIII). The reaction of (VIII) with Boc2O affords the N-protected compound (IX), which is alkylated with 3,5-bis(trifluoromethyl)benzyl bromide (X) and NaH to provide the benzyl ether (XI). Finally, this compound is N-deprotected by means of TFA to obtain the target piperidine.

1 Baker, R.; Harrison, T.; Swain, C.J.; Williams, B.J. (Merck Sharp & Dohme Ltd.); Azacyclic cpds., processes for their preparation and pharmaceutical compsns. containing them. EP 0528495; EP 0600952; JP 1994510034; WO 9304040 .
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) 10498 Benzaldehyde;Benzoic aldehyde;Phenylmethanal 100-52-7 C7H6O 详情 详情
(II) 64492 methyl 4-nitrobutanoate C5H9NO4 详情 详情
(III) 64493 5-nitro-6-phenyl-2-piperidinone C11H12N2O3 详情 详情
(IV) 64494 6-phenyl-2,5-piperidinedione C11H11NO2 详情 详情
(V) 64495 (cis),(trans)2-phenyl-3-piperidinol C11H15NO 详情 详情
(VI) 64496 (rac)(cis)3-hydroxy-2-phenylpiperidinium 4-methylbenzenesulfonate C18H23NO4S 详情 详情
(VII) 64497 (rac)(cis)[(2S,3S)-2-phenyl-3-piperidinol] C11H15NO 详情 详情
(VIII) 64498 (2S,3S)-2-phenyl-3-piperidinol C11H15NO 详情 详情
(IX) 64499 tert-butyl (2S,3S)-3-hydroxy-2-phenyl-1-piperidinecarboxylate C16H23NO3 详情 详情
(X) 27677 1-(bromomethyl)-3,5-bis(trifluoromethyl)benzene 32247-96-4 C9H5BrF6 详情 详情
(XI) 64500 tert-butyl (2S,3S)-3-{[3,5-bis(trifluoromethyl)benzyl]oxy}-2-phenyl-1-piperidinecarboxylate C25H27F6NO3 详情 详情
Extended Information