Methyl morpholine oxide → 3-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehyde

HRID 1506499Notes

Reaction equation

HRID 1506499 reaction equation
[C:1]1([N:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]3[O:20][N:19]=[C:18]4[C:21]5[C:26]([CH2:27][CH2:28][C:17]=34)=[CH:25][C:24]([CH:29]=C)=[CH:23][CH:22]=5)[CH:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[N+]1([O-])CC[O:35]CC1.I([O-])(=O)(=O)=O.[Na+]>C1COCC1.O.[Os](=O)(=O)(=O)=O>[C:1]1([N:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]3[O:20][N:19]=[C:18]4[C:21]5[C:26]([CH2:27][CH2:28][C:17]=34)=[CH:25][C:24]([CH:29]=[O:35])=[CH:23][CH:22]=5)[CH:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 3

HCID 82029Methyl morpholine oxideHCID 23667635Sodium periodateHCID 671704203-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole

Product 1

HCID 866699303-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehydeYield 100%

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a clear solution of 3-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole (Preparation 89A, 0.15 g, 0.368 mmol) in THF (1.5 mL) were added NMO (50% in water, 0.092 mL, 0.442 mmol) and osmium tetroxide (4% in water, 0.068 mL, 0.011 mmol) at room temperature. The solution was vigorously stirred at room temperature overnight. Sodium periodate (0.102 g, 0.479 mmol) in water (0.5 mL) was added. The mixture was stirred vigorously at room temperature under nitrogen for 30 min. Water (5 mL) was added and the mixture was extracted with ethyl acetate (3×2 mL). The combined ethyl acetate extracts were dried (sodium sulfate), filtered through a pad of silica gel which was then rinsed with ethyl acetate and concentrated to give 3-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehyde (0.15 g, 0.366 mmol, 100% yield) as a green solid. The compound had an HPLC retention time=3.64 min. (condition C); LC/MS M+1=409.9.

Workup

  1. stirringThe mixture was stirred vigorously at room temperature under nitrogen for 30 min
  2. extractionthe mixture was extracted with ethyl acetate (3×2 mL)
  3. dry with materialThe combined ethyl acetate extracts were dried (sodium sulfate)
  4. filtrationfiltered through a pad of silica gel which
  5. washwas then rinsed with ethyl acetate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ef28532d12ac42b69afcbf9e5d90d7b8
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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