反应详情

温度

30 °C

Crude erlotinib hydrochloride (37 gm, obtained in reference example 1), water (370 ml) and chloroform (370 ml) are taken into a reaction flask at 25-30° C. and start stirring. The contents are heated to 5-55° 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 added chloroform (200 ml) and methanol (60 ml) and stirred for 15 minutes at 50° C. (clear solution observed). Separated the layers at 50° C., the organic layer is washed with water (200 ml) at 50° C. and then combined the organic layers. To the organic layer added methanol (60 ml) dried over sodium sulfate and distilled the total solvent under vacuum at 50-55° C. To the residue added n-heptane (300 ml) and stirred for 30 minutes at 25-30° C. Filtered the material, washed with n-heptane (70 ml) and then dried the material at 60-65° C. under vacuum for 3 hours 30 minutes to give 34 gm of anhydrous erlotinib free base (HPLC Purity: 98.2%, Moisture Content: 0.2%).

1. stirringstirred for 15 minutes at 50° C. (clear solution not
2. stirringstirred for 15 minutes at 50° C. (clear solution observed)
3. customSeparated the layers at 50° C.
4. washthe organic layer is washed with water (200 ml) at 50° C.
5. additionTo the organic layer added methanol (60 ml)
6. dry with materialdried over sodium sulfate
7. distillationdistilled the total solvent under vacuum at 50-55° C
8. additionTo the residue added n-heptane (300 ml)
9. stirringstirred for 30 minutes at 25-30° C
10. filtrationFiltered the material
11. washwashed with n-heptane (70 ml)
12. customdried the material at 60-65° C. under vacuum for 3 hours 30 minutes