反应详情

温度

50 °C

To a stirred solution of O-desmethylvenlafaxine (13.17 g, 0.050 mol.) in tetrahydrofuran (300 mL) at 62–65° C., under a nitrogen atmosphere, was added 96 wt % formic acid (2.20 mL, d=1.22, 0.056 mol., 1.2 molar excess) in tetrahydrofuran (30 mL) dropwise over a period of 2 minutes, while maintaining the temperature in the range 62° C.–64° C. The solution was filtered through a pad of Celite filter aid (prewashed with tetrahydrofuran) and the filter pad was washed with hot (60–65° C.) tetrahydrofuran (2×20 mL). The filtrate and washings (temperature ˜35° C.) were warmed to 50° C. under a nitrogen atmosphere and allowed to cool. At 48° C. the stirred solution was seeded with crystals of O-desmethylvenlafaxine formate. Crystallization ensued immediately. When the slurry of crystals had cooled to 22° C. it was chilled to −5° C. to −10° C. The crystals were collected on a filter and washed with chilled (−5 to −10° C.) tetrahydrofuran (2×30 mL). After drying in a vacuum oven at room temperature under oil pump vacuum for 23 hours the product, O-desmethylvenlafaxine formate, weighed 13.79 g, (89% yield) and it had mp=149–150° C. It was characterized by DSC (sharp endotherm at 151.5° C.).

1. temperaturewhile maintaining the temperature in the range 62° C.–64° C
2. filtrationThe solution was filtered through a pad of Celite
3. filtrationfilter aid (prewashed with tetrahydrofuran)
4. washthe filter pad was washed with hot (60–65° C.) tetrahydrofuran (2×20 mL)
5. temperatureto cool
6. customAt 48° C.
7. customCrystallization
8. temperatureWhen the slurry of crystals had cooled to 22° C. it
9. temperaturewas chilled to −5° C. to −10° C
10. customThe crystals were collected on
11. filtrationa filter
12. washwashed
13. temperaturewith chilled (−5 to −10° C.) tetrahydrofuran (2×30 mL)
14. dry with materialAfter drying in a vacuum oven at room temperature under oil pump vacuum for 23 hours the product, O-desmethylvenlafaxine formate
15. customwas characterized by DSC (sharp endotherm at 151.5° C.)