Potassium Cyanide → tert-butyl (3RS,4RS)-4-(4-cyano-phenyl)-3-hydroxy-piperidine-1-carboxylate

Temperatur

60 °C

A suspension of 20 mg (0.30 mmol) of activated zinc powder, 76 mg (1.17 mmol) of potassium cyanide, 52 mg (0.20 mmol) of triphenylphosphine and 74 mg (0.10 mmol) of bis(triphenylphosphine)-nickel(II) dibromide in 2 ml of acetonitrile was heated at 60° C. under argon for 5 minutes. 356 mg (1.00 mmol) of tert-butyl (3RS,4RS)-4-(4-bromophenyl)-3-hydroxy-piperidine-1-carboxylate in solid form were added thereto. The green suspension was stirred at 60° C. under argon for 20 hours. The resulting dark brown suspension was filtered over Speedex and the insoluble material was washed with methylene chloride. The filtrate was partitioned between methylene chloride and 5% sodium hydrogen carbonate solution, the organic phase was dried over magnesium sulphate and finally the solvent was removed under reduced pressure. The crude product (416 mg) was purified by chromatography on silica gel with a 1:1 mixture of ethyl acetate and hexane as the eluent. There were obtained 168 mg (56% of theory) of tert-butyl (3RS,4RS)-4-(4-cyano-phenyl)-3-hydroxy-piperidine-1-carboxylate as a colourless solid; MS: 302 (M)+.

1. filtrationThe resulting dark brown suspension was filtered over Speedex
2. washthe insoluble material was washed with methylene chloride
3. customThe filtrate was partitioned between methylene chloride and 5% sodium hydrogen carbonate solution
4. dry with materialthe organic phase was dried over magnesium sulphate
5. customfinally the solvent was removed under reduced pressure
6. customThe crude product (416 mg) was purified by chromatography on silica gel with a 1:1 mixture of ethyl acetate and hexane as the eluent

ORD-Eintrag

ord-dfcd92635c5d4207a60d24ad221b36c5

Quelldatensatz

uspto-grants-2000_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06051712