Pyridine → 3-(3-Phenyl-4-(trifluoromethyl)isoxazol-5-yl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole

HRID 1506328Notes

Reaction equation

HRID 1506328 reaction equation
[C:1]1([C:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]3(O)[O:20][N:19]=[C:18]4[C:21]5[C:26]([CH2:27][CH2:28][CH:17]34)=[CH:25][C:24]([CH:29]=[CH2:30])=[CH:23][CH:22]=5)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)(Cl)=O.N1C=CC=CC=1>C1(C)C=CC=CC=1>[C:1]1([C:7]2[C:11]([C:12]([F:13])([F:14])[F:15])=[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]=[CH2:30])=[CH:23][CH:22]=5)[O:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 671707993-(3-Phenyl-4-(trifluoromethyl)isoxazol-5-yl)-7-vinyl-3,3a,4,5-tetrahydronaphtho[1,2-c]isoxazol-3-ol

Product 1

HCID 671720363-(3-Phenyl-4-(trifluoromethyl)isoxazol-5-yl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazoleYield 40.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

The 3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-7-vinyl-3,3a,4,5-tetrahydronaphtho[1,2-c]isoxazol-3-ol (5 g, 11.73 mmol) was mixed with thionyl chloride (1.712 mL, 23.45 mmol) and anhydrous toluene (80 mL). Pyridine (0.190 mL, 2.345 mmol) was then added dropwise. The mixture was stirred under nitrogen at room temperature for 30 min and 90° C. for 15 min. The mixture was concentrated under reduced pressure. The residue was partitioned between saturated aqueous sodium bicarbonate solution (50 mL) and dichloromethane (100 mL, 2×50 mL). The combined dichloromethane extracts were dried over sodium sulfate, filtered through a pad of silica gel and concentrated under reduced pressure. Flash chromatography purification (220 g silica gel column, 25→60% dichloromethane in hexanes) and trituration with methanol gave 3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole (1.96 g, 4.80 mmol, 40.9% yield) as a white solid. The compound had an HPLC retention time=4.28 min (condition C); LC/MS M+1=408.9.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customThe residue was partitioned between saturated aqueous sodium bicarbonate solution (50 mL) and dichloromethane (100 mL, 2×50 mL)
  3. dry with materialThe combined dichloromethane extracts were dried over sodium sulfate
  4. filtrationfiltered through a pad of silica gel
  5. concentrationconcentrated under reduced pressure
  6. customFlash chromatography purification (220 g silica gel column, 25→60% dichloromethane in hexanes) and trituration with methanol

Sources & evidence

ORD record
ord-4e46b10863f846b6998d3524b29faecd
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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