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

Temperature

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 record

ord-a3eaff7cd8824200a1038f4866032694

Source dataset

uspto-grants-2000_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06150526