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

HRID 749453Notes

Reaction equation

HRID 749453 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH2:28][CH:29]=C)[CH2:9][N:10]([CH3:27])[C:11](=[O:26])[C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]([C:22]([F:25])([F:24])[F:23])[CH:13]=2)=[CH:4][CH:3]=1.C[N+]1([O-])CC[O:35]CC1.OS([O-])=O.[Na+].I([O-])(=O)(=O)=O.[Na+]>CC(C)=O.C(O)(C)(C)C.O.[Cl-].[Na+].O.O=[Os](=O)(=O)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH2:28][CH:29]=[O:35])[CH2:9][N:10]([CH3:27])[C:11](=[O:26])[C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]([C:22]([F:25])([F:24])[F:23])[CH:13]=2)=[CH:4][CH:3]=1

Participants

10

Reactant 4

HCID 82029Methyl morpholine oxideHCID 23665763Sodium BisulfiteHCID 23667635Sodium periodateHCID 86606886N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-3,5-bis(trifluoromethyl)benzamide

Product 1

HCID 58683524N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-3,5-bis(trifluoromethyl)benzamide

Reagents, catalysts & solvents 5

HCID 30318Osmium TetroxideCatalystHCID 180AcetoneSolventHCID 962WaterSolvent3×HCID 6386tert-ButanolSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

N-[(2S)-2-(4-Fluorophenyl)pent-4-en-1-yl]-N-methyl-3,5-bis(trifluoromethyl)benzamide (570 mg, 1.32 mmol) was dissolved in a mixture of acetone (10 mL), t-butyl alcohol (5 mL) and water (2.5 mL). OsO4 (2.5% in t-butyl alcohol, 0.190 mL, 0.013 mmol) was added together with 4-methylmorpholine-4-oxide (680 mg, 5.8 mmol). The solution was stirred at room temperature overnight and then saturated aqueous solution of NaHSO3 (10 mL) was added. The mixture was stirred for 15 min, diluted with water (50 mL) and then extracted three times with CH2Cl2. The organic solution was washed with brine and then the solvent was evaporated. The residue (643 mg) was dissolved in a mixture of THF (7 mL) and water (3 mL) and to the resultant solution was added sodium periodate (309 mg, 1.45 mmol). The mixture was stirred at room temperature overnight, diluted with water (75 mL) and brine (40 mL) and then extracted three times with ethyl acetate. The combined organic solutions were washed three times with water, dried over Na2SO4 and then the solvent was evaporated. The product was purified by chromatography on silica gel using a mixture of heptane and ethyl acetate as eluent (1:1). There was obtained 398 mg (69%) of ) N-[(2S)-2-(4fluorophenyl)-4-oxobutyl]-N-methyl-3,5-bis(trifluoromethyl)benzamide as an oil. 1H NMR (400 MHz, CDCl3): 2.6-3.9 (cm, 8H), 6.8-7.6 (cm, 6H), 7.9 (s, 1H), 9.8 (s, 1H); LCMS: m/z 436 (M+1)+.

Workup

  1. stirringThe mixture was stirred for 15 min
  2. extractionextracted three times with CH2Cl2
  3. washThe organic solution was washed with brine
  4. customthe solvent was evaporated
  5. dissolutionThe residue (643 mg) was dissolved in a mixture of THF (7 mL) and water (3 mL) and to the resultant solution
  6. stirringThe mixture was stirred at room temperature overnight
  7. extractionextracted three times with ethyl acetate
  8. washThe combined organic solutions were washed three times with water
  9. dry with materialdried over Na2SO4
  10. customthe solvent was evaporated
  11. customThe product was purified by chromatography on silica gel using
  12. additiona mixture of heptane and ethyl acetate as eluent (1:1)

Sources & evidence

ORD record
ord-2fd5379c2e4544c5889b2d35f3f2e4ae
Source dataset
uspto-grants-2008_07
Patent number
US07402581B2

Reaction notes

Loading…