N-[(1R)-1-(4-Cyanophenyl)ethyl]carbamic acid tert-butyl este synthesis

Yield:-

Reaction Conditions:

Stage #1:[(R)-1-(4-bromo-phenyl)-ethyl]-carbamic acid tert-butyl ester;dicyanozinc in N,N-dimethyl-formamide for 1 h;
Stage #2:tetrakis(triphenylphosphine) palladium⁽⁰⁾ in N,N-dimethyl-formamide at 70 - 75; for 20.5 h;

Steps:

4
To a vial was charged tert-butyl [(1R)-1-(4-bromophenyl)ethyl]carbamate (4.3 gm), zinc cyanide (1.18 gm), and dimethylfomamide (13 mL). The mixture was purged with a stream of nitrogen then stirred under a nitrogen atmosphere for 1 hour. The reaction was then treated with palladium tetrakis(triphenylphosphine) (0.5 gm), sealed, and heated to 75 ⁰C for 3.5 hours. The reaction was then heated at 70 ⁰C for 17 hours. The mixture was cooled to room temperature and diluted with toluene (50 mL). Thiocyanuric acid (0.26 gm) was added followed by 3% aqueous sodium hydroxide (70 mL). The organic phase was washed again with a solution of thiocyanuric acid (0.26 gm) in 3% aqueous sodium hydroxide (70 mL). The organic phase was dried over sodium sulfate, filtered through a pad of Celite, concentrated under reduced pressure, and finally in vacuo to give a dark oil (3.9 gm). This material was diluted with dichloromethane and purified on a Biotage 65i column by elution with a gradient of 0-80% ethyl acetate/heptanes to give the title compound as a colorless oil (3.0 gm): ¹H NMR (400 MHz, CDCI₃) δ ppm 7.52 - 7.69 (2 H, m), 7.41 (2 H, m), 4.83 (2 H, m), 1.21 - 1.52 (12 H, m).

References:

PFIZER INC. WO2009/60278, 2009, A1 Location in patent:Page/Page column 48