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【结 构 式】

【分子编号】52669

【品名】2-methyl-2-propanaminium 3-cyano-5-methyl-3-hexenoate

【CA登记号】

【 分 子 式 】C12H22N2O2

【 分 子 量 】226.31896

【元素组成】C 63.69% H 9.8% N 12.38% O 14.14%

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:(VIIb)

An asymmetric synthesis of pregabalin has been reported: Condensation of isobutyraldehyde (I) with acrylonitrile (II) by means of DBU and 2,6-di-tert-butyl-4- methylphenol (DBP) gives 3-hydroxy-4-methyl-2-methylenepentanenitrile (III), which is acylated with AcCl or Ac2O and pyridine to yield the acetate (IV). The carboxylation of (IV) by means of Pd(OAc)2, PPh3, CO and EtOH affords 3-cyano-4-methyl-3-hexenoic acid ethyl ester (Va-b), which is hydrolyzed with KOH in THF/water to provide the corresponding carboxylic acid potassium salt (VIa-b). Acidification of (VIa-b) with HCl, followed by reaction with tert-butylamine gives the corresponding salt (VIIa-b), which is reduced with H2 over a chiral (R,R)-rhodium catalyst [(R,R)-Rh] in THF/water to yield (S)-3-cyano-5-methylhexanoic acid butylammonium salt (VIII). Finally, the CN group of (VIII) is reduced with H2 over a sponge-Ni catalyst in basic (KOH) ethanol. Alternatively, intermediate (VIa-b) can be reduced with H2 over a chiral (R,R)-rhodium catalyst [(R,R)-Rh] in THF/water to yield (S)-3-cyano-5-methylhexanoic acid potassium salt (IX). Finally, the CN group of (IX) is reduced with H2 over a sponge-Ni catalyst in basic (KOH) ethanol.

1 Mich, T.F.; Goel, O.P.; Mulhern, T.A.; Burk, M.J.; Hoekstra, M.S.; Ramsden, J.A. (Pfizer Inc.); Asymmetric synthesis of pregabalin. WO 0155090 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(Va) 52664 ethyl 3-cyano-5-methyl-3-hexenoate C10H15NO2 详情 详情
(Vb) 52665 ethyl 3-cyano-5-methyl-3-hexenoate C10H15NO2 详情 详情
(VIa) 52666 potassium 3-cyano-5-methyl-3-hexenoate C8H10KNO2 详情 详情
(VIb) 52667 potassium 3-cyano-5-methyl-3-hexenoate C8H10KNO2 详情 详情
(VIIa) 52668 2-methyl-2-propanaminium 3-cyano-5-methyl-3-hexenoate C12H22N2O2 详情 详情
(VIIb) 52669 2-methyl-2-propanaminium 3-cyano-5-methyl-3-hexenoate C12H22N2O2 详情 详情
(I) 13226 2-Methylpropanal; Isobutyraldehyde 78-84-2 C4H8O 详情 详情
(II) 10847 Acrylonitrile 107-13-1 C3H3N 详情 详情
(III) 52660 2-(1-hydroxy-2-methylpropyl)-2-propenenitrile C7H11NO 详情 详情
(IV) 52661 2-cyano-1-(1-methylethyl)-2-propenyl acetate C9H13NO2 详情 详情
(VIII) 52662 2-methyl-2-propanaminium 3-cyano-5-methylhexanoate C12H24N2O2 详情 详情
(IX) 52663 potassium 3-cyano-5-methylhexanoate C8H12KNO2 详情 详情
Extended Information