乙基 4-(氰甲基)哌啶-4-羧酸乙酯

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-Cyanomethyl-piperidine-4-carboxylic acid ethyl ester (14.2 g) was dissolved in pyridine (150 ml), 2-chlorobenzenesulfonyl chloride (16.83 g) was added and the reaction mixture was stirred overnight at RT. Then, most of pyridine was evaporated off in vacuo, the residue was dissolved in AcOEt, washed with 0.5M aqueous HCl and brine. The organic layer was dried over magnesium sulphate and concentrated in vacuo. The residue (crude oil) was chromatographed over silica (AcOEt/Heptanes, gradient from 0 to 25%) to give the desired material (8.5 g) as viscous brown oil. MS (ESI): 388.1 (M+NH4)+. Then, most of pyridine was evaporated off in vacuo the residue was dissolved in AcOEt washed with 0.5M aqueous HCl and brine The organic layer was dried over magnesium sulphate concentrated in vacuo The residue (crude oil) was chromatographed over silica (AcOEt/Heptanes, gradient from 0 to 25%)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-Cyanomethyl-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (36 g) was dissolved in methylene chloride (600 ml), cooled to 0° C. then trifluoroacetic acid (207.8 g, 134.9 ml) was added under an argon atmosphere and the mixture was stirred over night allowing the temperature of the reaction mixture to rise to RT. The reaction mixture was then concentrated in vacuo, the residue taken up in methylene chloride and washed several times with 1M aqueous NaOH (to pH 12). The layers were separated, the organic layer washed with brine, dried over sodium sulphate and concentrated to give 4-cyanomethyl-piperidine-4-carboxylic acid ethyl ester a brown oil (14.2 g) which was essentially pure according to NMR and used in next reaction step without further purification. MS (ESI): 197.2 (MH+). to rise to RT The reaction mixture was then concentrated in vacuo washed several times with 1M aqueous NaOH (to pH 12) The layers were separated the organic layer washed with brine dried over sodium sulphate concentrated