Thionyl Chloride → (2R)-3-Bromo-2-hydroxy-2-methyl-N-(4-cyano-3-methylphenyl)propion-amide

Participants

Reaction Conditions

Reaction Steps

(2R)-3-Bromo-2-hydroxy-2-methylpropionic acid (1.52 g, 8.3 mmol) was dissolved in 35 ml of dry THF and 0.5 ml of dry DMA was added. Solution was cooled to 0° C. and thionyl chloride (0.8 ml; 10.8 mmol) was added dropwise. The solution was allowed to heat up to room temperature and stirred for 2 hours at room temperature. 4-Cyano-3-methylaniline (1.07 g, 8.1 mmol) was added in 5 ml of dry THF and reaction refluxed for 2 hours. THF was evaporated, the residue dissolved in 40 ml of CH2Cl2 and washed with 50 ml of 1% NaHCO3 and then with 4×25 ml of water. The organic phase was evaporated and residue was dried under reduced pressure at 40° C. overnight to give 2.24 g of crude product which was crystallized from 5 ml of toluene (75° C. then cooled to room temperature and to 0° C.), filtered and washed with 5 ml of ice cold toluene. The precipitate was dried under reduced pressure overnight at 40° C. to give 1.54 g of the product.

Provenance & Evidence