Formic Acid → O-Desmethylvenlafaxine Formate

HRID 860917Notes

Reaction equation

HRID 860917 reaction equation
[CH3:1][N:2]([CH2:4][CH:5]([C:13]1([OH:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:6]1[CH:7]=[CH:8][C:9]([OH:12])=[CH:10][CH:11]=1)[CH3:3].[CH:20]([OH:22])=[O:21]>O1CCCC1>[CH3:1][N:2]([CH2:4][CH:5]([C:13]1([OH:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:6]1[CH:7]=[CH:8][C:9]([OH:12])=[CH:10][CH:11]=1)[CH3:3].[CH:20]([O-:22])=[O:21]

Participants

4

Reactant 2

HCID 284Formic AcidHCID 125017Desvenlafaxine

Product 1

HCID 86603914O-Desmethylvenlafaxine FormateYield 89%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

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.).

Workup

  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. custommp=149 150° C
  16. customwas characterized by DSC (sharp endotherm at 151.5° C.)

Sources & evidence

ORD record
ord-be5e7601a3bb4cdfa9e2f857013ce72a
Source dataset
uspto-grants-2006_12
Patent number
US07154001B2

Reaction notes

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