Water → Erlotinib

Participants

Reaction Conditions

Reaction Steps

Crude erlotinib hydrochloride (37 gm, obtained in step-I), water (370 ml) and chloroform (370 ml) are taken into a reaction flask at 25-30° C. and stirring begun. The contents are heated to 50-55° C., sodium hydroxide solution is added at 50-55° C. and then stirred for 15 minutes at 50° C. (clear solution not observed). To the reaction mass is added chloroform (200 ml) and methanol (60 ml) and stirred for 15 minutes at 50° C. (clear solution observed). The layers are separated at 50° C., the organic layer is washed with water (200 ml) at 50° C. and then the organic layers are combined. To the organic layer is added methanol (60 ml) and then dried over sodium sulfate and the total solvent is distilled under vacuum at 50-55° C. To the residue is added n-heptane (300 ml) and stirred for 30 minutes at 25-30° C. The material, is filtered washed with n-heptane (70 ml) and then the material is dried at 60-65° C. under vacuum for 3 hours 30 minutes to give 34 gm of erlotinib free base [HPLC purity: 98.2%; Content of N-methoxyethyl impurity: 0.24% (at 1.14 RRT)].

Provenance & Evidence