反应详情

温度

45 °C

To a stirred suspension of O-desmethylvenlafaxine (39.51 g, 0.150 mol) in acetone (1500 mL) at 55–60° C., under a nitrogen atmosphere, was added a solution of 96% formic acid (13.5 mL, d=1.22, 2.29 molar excess) in acetone (150 mL) over a period of 10 min. The stirred mixture was kept at 55–60° C. for a further 5 min. to complete the dissolution. The warm solution was filtered through a pad of Celite filter aid (prewashed with warm acetone) and the filter pad was washed with warm acetone (150 mL). The filtrate and washings (temperature ˜35° C.) were warmed to 45° C. under a nitrogen atmosphere and seeded with crystals of O-desmethyl-venlafaxine formate. The stirred solution was allowed to cool. Crystallization ensued and was copious after 1 hour (when the temperature had fallen to 30° C.). The slurry of crystals at 27° C. was chilled to −10° C. over a period of half an hour and maintained at −5–−10° C. for 15 min. The crystals were then collected on a filter and washed with chilled (−5 to −10° C.) acetone (2×100 mL). After drying in a vacuum oven at room temperature under oil pump vacuum for 24 hours, the product, O-desmethyl-venlafaxine formate, weighed 38.5 g, (83% yield) and it had mp=148° C.–149.5° C. It was characterized by DSC (sharp endotherm at 152.4° C.).

1. dissolutionthe dissolution
2. filtrationThe warm solution was filtered through a pad of Celite
3. filtrationfilter aid (prewashed with warm acetone)
4. washthe filter pad was washed with warm acetone (150 mL)
5. temperatureto cool
6. customCrystallization
7. waitwas copious after 1 hour
8. customhad fallen to 30° C.
9. temperatureThe slurry of crystals at 27° C. was chilled to −10° C. over a period of half an hour
10. temperaturemaintained at −5–−10° C. for 15 min
11. customThe crystals were then collected on
12. filtrationa filter
13. washwashed
14. temperaturewith chilled (−5 to −10° C.) acetone (2×100 mL)
15. customAfter drying in a vacuum oven at room temperature under oil pump vacuum for 24 hours
16. customwas characterized by DSC (sharp endotherm at 152.4° C.)