Methyl morpholine oxide → 3-cyano-N-[2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-1-naphthamide

HRID 749444Notes

Reaction equation

HRID 749444 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:13]([N:15]([CH2:17][CH:18]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:19][CH:20]=C)[CH3:16])=[O:14])[C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2)#[N:2].C[N+]1([O-])CC[O:33]CC1.S(=O)(O)[O-].[Na+].I([O-])(=O)(=O)=O.[Na+]>CC(C)=O.C(O)(C)(C)C.O.C1COCC1.[Cl-].[Na+].O.O=[Os](=O)(=O)=O>[C:1]([C:3]1[CH:4]=[C:5]([C:13]([N:15]([CH2:17][CH:18]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:19][CH:20]=[O:33])[CH3:16])=[O:14])[C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2)#[N:2]

Participants

11

Reactant 4

HCID 82029Methyl morpholine oxideHCID 23665763Sodium BisulfiteHCID 23667635Sodium periodateHCID 689791393-cyano-N-[2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-1-naphthamide

Product 1

HCID 111530243-cyano-N-[2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-1-naphthamideYield 95%

Reagents, catalysts & solvents 6

HCID 30318Osmium TetroxideCatalystHCID 180AcetoneSolventHCID 962WaterSolvent3×HCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

3-Cyano-N-[2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-1-naphthamide (1.5 g, 4.03 mmol) was dissolved in a mixture of acetone (30 mL), tert-butanol (15 mL) and water (7.5 mL) and stirred at room temperature during addition of OsO4 (0.40 mL of 2.5% in tert-butanol, 0.04 mmol). 4-Methylmorpholine N-oxide (2.08 g, 17.8 mmol) was added and the mixture was stirred at room temperature overnight. A saturated aqueous solution of sodium bisulfite (15 mL) was added and the mixture stirred for 5 min and then concentrated. The residue was diluted with water (100 mL) and then extracted thrice with CH2Cl2. The combined organic solutions were washed with brine and the solvent removed by evaporation. The residue was dissolved in a mixture of THF (21 mL) and water (7 mL) whereupon sodium periodate (0.95 g, 4.43 mmol) was added. The solution was stirred at room temperature overnight and then diluted with water (150 mL) and brine (75 mL). The mixture was extracted thrice with ethyl acetate and the combined organic solutions were washed with water and then with brine. The solvent was removed by evaporation and the residue flash chromatographed on silica gel (ethyl acetate-heptane, 7:3). There was obtained 1.43 g (95%) of 3-cyano-N-[2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-1-naphthamide as a colourless oil. 1H NMR (400 MHz, CDCl3): 2.4-4.4 (cm, 8H), 6.8-8.0 (cm, 9H), 8.2 (s, 1H), 9.8 (s, 1H).

Workup

  1. stirringthe mixture stirred for 5 min
  2. concentrationconcentrated
  3. additionThe residue was diluted with water (100 mL)
  4. extractionextracted thrice with CH2Cl2
  5. washThe combined organic solutions were washed with brine
  6. customthe solvent removed by evaporation
  7. additionwas added
  8. stirringThe solution was stirred at room temperature overnight
  9. extractionThe mixture was extracted thrice with ethyl acetate
  10. washthe combined organic solutions were washed with water
  11. customThe solvent was removed by evaporation
  12. customthe residue flash chromatographed on silica gel (ethyl acetate-heptane, 7:3)

Sources & evidence

ORD record
ord-75c197756f394ef6a09123e31a71ea56
Source dataset
uspto-grants-2008_07
Patent number
US07402581B2

Reaction notes

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