Formic Acid → O-Desmethylvenlafaxine Formate

HRID 891033Notes

Reaction equation

HRID 891033 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]>CC(C)=O>[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 83%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Conditions

Temperature
45 °C

Procedure

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.).

Workup

  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.)

Sources & evidence

ORD record
ord-3ceadfdceb5748e4a3e1e43e9072ecdf
Source dataset
uspto-grants-2006_02
Patent number
US07001920B2

Reaction notes

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