【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% |
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 |