Hydrochloric Acid → Erlotinib Hydrochloride

Participants

Reaction Conditions

Reaction Steps

In a 2.0 liter, 4 neck, round bottom flask equipped with a mechanical stirrer, a thermometer pocket and a reflux condenser, 420 ml of 1-pentanol (16.8 volumes with respect to erlotinib base) and 25 g (0.0635 mol) of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine (erlotinib base) was charged at 25-30° C. under stirring. The reaction mixture was then cooled to 20-25° C. to obtain a suspension. 30 ml of 1-pentanol-HCl solution (prepared by scrubbing HCl gas into 1-pentanol to a concentration by assay of 16-18% (w/w)) was added drop wise over a period of 15 minutes at a temperature of 20-25° C. The reaction mixture was stirred for a further 1 hour. The product was isolated by filtration, washed with 25 ml of 1-pentanol, and dried under reduced pressure (50 mm Hg) at 50-55° C., to give 25 g of erlotinib hydrochloride polymorph A (loss on drying <0.5%).

Provenance & Evidence