反应详情

温度

35 °C

A solution of phenyl hydrazine (1.29 g, 12.0 mmol) and trifluoroacetic acid (3.0 mL) in a 49:1 solution of toluene:acetonitrile (50 mL) is heated at 35° C. 4-Formyl-piperidine-1-carboxylic acid benzyl ester (2.7 g, 10.91 mmol) is dissolved in a 49:1 solution of toluene:acetonitrile (10 mL) and added dropwise to the mixture (WO2005046682). The mixture is stirred at 35° C. overnight. The resulting solution is cooled to 0° C., and methanol (5 mL) is added. NaBH4 (0.619 g, 16.38 mmol) is added portion wise to the solution and the mixture is stirred for 45 min. The reaction mixture is washed with aqueous NH4OH (6%, 25 mL) and brine (30 mL), dried over sodium sulfate, and evaporated to dryness to give a yellow solid. The crude solid is recrystallised from EtOAc to give a yellow solid (1.25 g, 1st crop). The mother liquor is evaporated and purified by silica gel chromatography, eluting with hexane:ethyl acetate (8:2) to give the title compound as a pale yellow solid (1.2 g, 2nd crop) with a total yield of (2.4 g, 76%). ESI/MS m/z 323 (M+H)+.

1. temperatureThe resulting solution is cooled to 0° C.
2. stirringthe mixture is stirred for 45 min
3. washThe reaction mixture is washed with aqueous NH4OH (6%, 25 mL) and brine (30 mL)
4. dry with materialdried over sodium sulfate
5. customevaporated to dryness
6. customto give a yellow solid
7. customThe crude solid is recrystallised from EtOAc
8. customto give a yellow solid (1.25 g, 1st crop)
9. customThe mother liquor is evaporated
10. custompurified by silica gel chromatography
11. washeluting with hexane:ethyl acetate (8:2)