Methyl morpholine oxide → 3-bromo-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-5-(trifluoromethyl)benzamide

HRID 2063305Notes

Reaction equation

HRID 2063305 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[C:5]([N:7]([CH2:9][C@H:10]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[CH2:11][CH:12]=C)[CH3:8])=[O:6].C[N+]1([O-])CC[O:32]CC1.OS([O-])=O.[Na+]>CC(C)=O.O.O=[Os](=O)(=O)=O>[Br:1][C:2]1[CH:3]=[C:4]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[C:5]([N:7]([CH2:9][C@H:10]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[CH2:11][CH:12]=[O:32])[CH3:8])=[O:6]

Participants

7

Reactant 3

HCID 82029Methyl morpholine oxideHCID 161193783-bromo-N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-5-(trifluoromethyl)benzamideHCID 23665763Sodium Bisulfite

Product 1

HCID 159506583-bromo-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-5-(trifluoromethyl)benzamideYield 92%

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 180AcetoneSolventHCID 962WaterSolvent2×

Procedure

To a solution of 3-bromo-N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-5-(trifluoromethyl)benzamide (0.86 g, 1.9 mmol) in acetone (45 mL) were added OsO4 (2.5% in t-butyl alcohol, 0.49 mL, 0.039 mmol) and 4-methylmorpholine-4-oxide (0.41 g, 3.5 mmol). The solution was stirred under nitrogen at RT overnight and then an aqueous solution of NaHSO3 (39%, 45 mL) was added. The mixture was stirred for 2 h, diluted with water and then extracted twice with methylene chloride. The combined organic solutions were separated by means of a phase separator column and the solvent was removed by evaporation. The residue (1.08 g) was dissolved in THF (18 mL) and water (4.5 mL) and to the resultant solution was added NaIO4 (0.73 g, 3.4 mmol). The mixture was stirred under nitrogen overnight at RT. The mixture was partitioned between methylene chloride and water. The aqueous phase was extracted with methylene chloride and then the combined organic solutions were washed with brine and separated by means of a phase separator column. The solvent was removed by evaporation and there was obtained 0.78 g (90%) of the title compound. 1H NMR (500 MHz, CDCl3): 2.4-4.4 (cm, 8H), 6.8-7.8 (cm, 7H), 9.8 (s, 1H); LCMS: m/z 447 (M−1)+.

Workup

  1. stirringThe mixture was stirred for 2 h
  2. extractionextracted twice with methylene chloride
  3. customThe combined organic solutions were separated by means of a phase separator column
  4. customthe solvent was removed by evaporation
  5. dissolutionThe residue (1.08 g) was dissolved in THF (18 mL)
  6. stirringThe mixture was stirred under nitrogen overnight at RT
  7. customThe mixture was partitioned between methylene chloride and water
  8. extractionThe aqueous phase was extracted with methylene chloride
  9. washthe combined organic solutions were washed with brine
  10. customseparated by means of a phase separator column
  11. customThe solvent was removed by evaporation

Sources & evidence

ORD record
ord-4857b15308624d2b90a24a6ab0be4e47
Source dataset
uspto-grants-2012_10
Patent number
US08288370B2

Reaction notes

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