Methyl morpholine oxide → 3,5-dichloro-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methylbenzamide

HRID 749455Notes

Reaction equation

HRID 749455 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:21]=[C:22]([Cl:24])[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:29]CC1.OS([O-])=O.[Na+].I([O-])(=O)(=O)=O.[Na+]>CC(C)=O.C(O)(C)(C)C.O.O=[Os](=O)(=O)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:21]=[C:22]([Cl:24])[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:29])[CH3:8])=[O:6]

Participants

9

Reactant 4

HCID 82029Methyl morpholine oxideHCID 23665763Sodium BisulfiteHCID 23667635Sodium periodateHCID 689786383,5-Dichloro-N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methylbenzamide

Product 1

HCID 112455783,5-dichloro-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methylbenzamideYield 69.6%

Reagents, catalysts & solvents 4

HCID 30318Osmium TetroxideCatalystHCID 180AcetoneSolventHCID 962WaterSolvent3×HCID 6386tert-ButanolSolvent

Procedure

3,5-Dichloro-N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methylbenzamide (210 mg, 0.57 mmol) was dissolved in a mixture of acetone (4 mL), t-butyl alcohol (2 mL) and water (1 mL). OsO4 (2.5% in t-butyl alcohol, 0.080 mL, 0.006 mmol) was added together with 4-methylmorpholine-4-oxide (296 mg, 2.52 mmol). The solution was stirred under nitrogen at room temperature overnight and then an aqueous solution of NaHSO3 (39%, 6 mL) was added. The mixture was stirred for 30 min, diluted with water (25 mL) and then extracted twice with CH2Cl2. The organic solution was dried over Na2SO4 and then the solvent was evaporated. The residue (256 mg) was dissolved in a mixture of THF (3 mL) and water (1 mL) and to the resultant solution was added sodium periodate (135 mg, 0.63 mmol). The mixture was stirred at room temperature overnight, diluted with water (25 mL) and then extracted twice CH2Cl2. The combined organic solutions were dried over Na2SO4 and then the solvent was evaporated. There was obtained 146 mg (69%) of 3,5-dichloro-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methylbenzamide as an oil. 1H NMR (400 MHz, CDCl3): 2.6-3.9 (cm, 8H), 6.4-7.4 (cm, 7H), 9.8 (s, 1H); LCMS: m/z 369 (M+1)+.

Workup

  1. stirringThe mixture was stirred for 30 min
  2. extractionextracted twice with CH2Cl2
  3. dry with materialThe organic solution was dried over Na2SO4
  4. customthe solvent was evaporated
  5. dissolutionThe residue (256 mg) was dissolved in a mixture of THF (3 mL) and water (1 mL) and to the resultant solution
  6. stirringThe mixture was stirred at room temperature overnight
  7. extractionextracted twice CH2Cl2
  8. dry with materialThe combined organic solutions were dried over Na2SO4
  9. customthe solvent was evaporated

Sources & evidence

ORD record
ord-8298b7231c6040b092bbc1cae4078ed4
Source dataset
uspto-grants-2008_07
Patent number
US07402581B2

Reaction notes

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