Imidazole → HCID 67457927, compound

Participants

Reaction Steps

A solution of ethyl 3-(4-chlorophenyl)-2-cyanoacrylate (6.2 g, 26 mmol) in 2-propanol (80 mL) was added dropwise to a stirred suspension of NaBH4 (2.8 g, 74 mmol) in 2-propanol (20 mL). The mixture was stirred at room temperature overnight. Excess NaBH4 was destroyed with saturated NH4Cl, and most of the 2-propanol was removed in vacuo. The residue was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated. The crude 2-(4-chlorobenzyl)-3-hydroxypropanenitrile was used without purification. TBS-Cl (2.77 g, 18.4 mmol) in dry DMF (15 mL) was added to a solution of the crude 2-(4-chlorobenzyl)-3-hydroxypropanenitrile (3.00 g, 15.3 mmol) and imidazole (4.18 g, 61.3 mmol) in DMF (25 mL) at 0° C. under nitrogen. The reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was partitioned between ether and water. The organic layer was washed with brine, dried and concentrated. The residue was purified by column (hexanes:EtOAc, 30:1) to give 3-(tert-butyldimethylsilyloxy)-2-(4-chlorobenzyl)propanenitrile (3.70 g, 78%) as a colorless oil.

Provenance & Evidence