反应 #1726679

反应方程式

Bu3SnH

AIBN

Methyl Chloro-oxo-acetate

1-tert-butoxycarbonyl-4-[2-(4-methylphenylsulfanyl)phenyl]piperidin-4-ol

→

piperidine-1-carboxylic acid tert-butyl ester

收率 139.6%

溶剂

Ethyl acetate

CHCl3

CH3CN

反应条件

后处理

1. 1
   其他to reach room temperature
2. 2
   其他some salts were removed by filtration through celite
3. 3
   洗涤The organic phase was washed with sat. NaHCO3 (140 ml), brine (140 mL)
4. 4
   干燥dried (MgSO4)
5. 5
   其他The solvents were evaporated in vacuo
6. 6
   干燥the crude material was dried in vacuo
7. 7
   workup.DISSOLUTIONThis material was dissolved in dry toluen (48 mL) under argon
8. 8
   workup.STIRRINGThe solution was stirred under argon at 90° C. for 2.5 h
9. 9
   其他The solvent was evaporated in vacuo
10. 10
    其他the crude material was purified by flash chromatography on silicagel (eluent

实验过程

Methyl Chloro-oxo-acetate (1.37 g, 11.25 mmol) was added to a stirred solution of 1-tert-butoxycarbonyl-4-[2-(4-methylphenylsulfanyl)phenyl]piperidin-4-ol (3.00 g, 7.5 mmol) and 4-(dimethylamino)pyridine (1.65 g, 13.5 mmol) in a mixture of dry CH3CN (24 ml) and CHCl3 (12 mL) at 0° C. under argon. The reaction mixture was allowed to reach room temperature and then stirred 2 h. Ethyl acetate (140 mL) was added and some salts were removed by filtration through celite. The organic phase was washed with sat. NaHCO3 (140 ml), brine (140 mL) and dried (MgSO4). The solvents were evaporated in vacuo and the crude material was dried in vacuo. This material was dissolved in dry toluen (48 mL) under argon. Bu3SnH (3.27 g, 11.25 mmol) and AIBN (0.31 g, 1.88 mmol) were added. The solution was stirred under argon at 90° C. for 2.5 h. The solvent was evaporated in vacuo, and the crude material was purified by flash chromatography on silicagel (eluent: a stepwise gradient of ethylacetat in heptane from 10:90 to 20:80) to produce 44244-methylphenylsulfanyl)phenyl)-piperidine-1-carboxylic acid tert-butyl ester as a clear oil (1.94 g, 67%). This oil was dissolved in MeOH (9.2 mL) and HCl in diethylether (2.0 M) was added at 0° C. The reaction mixture was allowed to warm to room temperature and stirred overnight. The target compound was collected as its hydrochloride. M.p 229-231° C. Calculated for C18H21NS.HCl: C, 67.58; H, 6.63; N, 4.38. Found: C, 67.33; H, 6.97; N, 4.31. LC/MS (m/z) 284 (MH+); RT=2.12; purity (UV, ELSD): 96%, 100%; yield: 0.26 g (46%).

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