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

HRID 1506447Notes

Reaction equation

HRID 1506447 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]2(O)[O:20][N:19]=[C:18]3[C:21]4[C:26]([CH2:27][CH2:28][CH:17]23)=[CH:25][C:24]([CH:29]=[CH2:30])=[CH:23][CH:22]=4)[O:9][N:8]=1.S(Cl)(Cl)=O.N1C=CC=CC=1>C1(C)C=CC=CC=1>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[C:11]([C:12]([F:14])([F:15])[F:13])=[C:10]([C:16]2[O:20][N:19]=[C:18]3[C:21]4[C:26]([CH2:27][CH2:28][C:17]=23)=[CH:25][C:24]([CH:29]=[CH2:30])=[CH:23][CH:22]=4)[O:9][N:8]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 671699583-(3-(Pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-7-vinyl-3,3a,4,5-tetrahydronaphtho[1,2-c]isoxazol-3-ol

Product 1

HCID 671704663-(3-(Pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazoleYield 125.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred suspension of 3-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-7-vinyl-3,3a,4,5-tetrahydronaphtho[1,2-c]isoxazol-3-ol (Preparation 63E, 0.081 g, 0.190 mmol) in anhydrous toluene (2.0 mL) at room temperature was added thionyl chloride (0.028 mL, 0.379 mmol) followed by pyridine (3.07 μl, 0.038 mmol). The reaction mixture was stirred at room temperature for 30 min. and then at 80° C. for 15 min. The reaction mixture was cooled to room temperature and concentrated. The solid residue was diluted with dichloromethane (30 mL), washed with a saturated aqueous solution of sodium bicarbonate (10 mL), and dried over anhydrous sodium sulfate. Concentration under reduced pressure afforded a tan solid. The crude products were combined and triturated with methanol with sonication. The solid was collected to provide 3-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole (0.098 g, 0.239 mmol, 64% yield) as a tan solid. The product had an HPLC with a ret. time=3.36 min.−Column: Chromolith SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=409.9.

Workup

  1. waitat 80° C. for 15 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationconcentrated
  4. additionThe solid residue was diluted with dichloromethane (30 mL)
  5. washwashed with a saturated aqueous solution of sodium bicarbonate (10 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationConcentration under reduced pressure
  8. customafforded a tan solid
  9. customtriturated with methanol with sonication
  10. customThe solid was collected

Sources & evidence

ORD record
ord-91eccf527b924930a258dc29f86bd46f
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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