Benzyl Alcohol → Benzyl 2-bromo-4-chlorobutyrate

Participants

Reaction Conditions

Reaction Steps

Heptanes (1.5 L) and calcium carbonate (150 g; 1.50 mol) were added to the distillation residue from step (a) above and benzyl alcohol (236.8 g; 2.19 mol) was added with stirring at 23-25° C. After stirring for 3.5 hours at 23-25° C., GC analysis indicated approximately 20% of unreacted acyl chloride. After additional stirring for 20 hours, approximately 10% of unreacted acyl chloride was estimated to be present by GC. The resultant mixture was filtered, and the filter cake was washed with heptanes (600 mL). Tetrahydrofuran (200 mL) and a 6% aqueous sodium hydrogen carbonate solution (400 mL) were added to the combined filtrates, and the mixture was stirred for 1 hour at room temperature. The aqueous phase (pH approximately 1) was separated and discarded. The organic phase was washed with water (400 mL) and concentrated at 60° C. under vacuum (down to 25 mmHg). GC analysis on the residue (497.7 g; 85% yield), indicated approximately 7% of unreacted acyl chloride. The hydrolysis of unreacted starting material was forced to completion by addition of further heptanes (1.52 L), tetrahydrofuran (150 mL) and 6% aqueous sodium hydrogen carbonate (600 mL). After stirring for 1 hour at room temperature, less than 1% unreacted acyl chloride was estimated to be present by GC. The aqueous phase (pH approximately 8) was separated and discarded. The organic phase was washed with water (200 mL) and concentrated at 65° C. under vacuum (down to 25 mmHg). This resulted in 418.1 g (72%) of crude title compound as a tea coloured residual oil.

Provenance & Evidence