Reaktion #1726679

Reaktionsgleichung

Bu3SnH

AIBN

Methyl Chloro-oxo-acetate

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

→

piperidine-1-carboxylic acid tert-butyl ester

Ausbeute 139.6%

Lösungsmittel

Ethyl acetate

CHCl3

CH3CN

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeto reach room temperature
2. 2
   Sonstigesome salts were removed by filtration through celite
3. 3
   WaschenThe organic phase was washed with sat. NaHCO3 (140 ml), brine (140 mL)
4. 4
   Trocknendried (MgSO4)
5. 5
   SonstigeThe solvents were evaporated in vacuo
6. 6
   Trocknenthe 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
   SonstigeThe solvent was evaporated in vacuo
10. 10
    Sonstigethe crude material was purified by flash chromatography on silicagel (eluent

Vorschrift

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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