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

HRID 1506333
Notes
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Reaction equation

HRID 1506333 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:28](=[CH:29][CH:30]=1)[C:9]1=[N:10][O:11][C:12]([C:13]3[O:17][N:16]=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:14]=3[C:24]([F:27])([F:26])[F:25])=[C:8]1[CH2:7][CH2:6]2>ClCCl>[C:18]1([C:15]2[C:14]([C:24]([F:27])([F:26])[F:25])=[C:13]([C:12]3[O:11][N:10]=[C:9]4[C:28]5[C:5]([CH2:6][CH2:7][C:8]=34)=[CH:4][C:3]([OH:2])=[CH:30][CH:29]=5)[O:17][N:16]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

3

Reactant 1

HCID 671703377-Methoxy-3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[1,2-c]isoxazole

Product 1

HCID 1360658093-(3-Phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-olYield 39.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 7-methoxy-3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[1,2-c]isoxazole (Preparation 8A, 0.125 g, 0.303 mmol) in dichloromethane (4 mL) was added borontribromide (1.0 M in dichloromethane, 3.03 mL, 3.03 mmol) at 0° C. over a period of 3 min. The contents were allowed to come to room temperature over a period of 15 min. and stirred at room temperature for 1 h. Additional borontribromide (4 mL) was added at room temperature over a period of 2 min. and the reaction was stirred for 3 h. The reaction mixture was concentrated and kept on the high vacuum pump for 10 min. Dichloromethane (5 mL) was added followed by 3 mL of borontribromide at room temperature. The contents were stirred at room temperature for 60 h. The reaction mixture was cooled to 0° C. and quenched by the slow addition of methanol (˜0 mL). The contents were stirred for 10 min. and concentrated under reduced pressure. The resulting residue was partitioned between dichloromethane (25 mL) and water (10 mL). The dichloromethane layer was washed with brine (20 mL), dried over sodium sulfate and concentrated. The resulting solid was triturated with ethyl acetate (5 mL), collected by filtration, washed with ethyl acetate (2×3 mL) and dried to yield 3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-ol (0.050 g, 0.119 mmol, 39.3% yield) as a white solid. The compound had an HPLC retention time=3.77 min (condition C); LC/MS M+1=399.

Workup

  1. additionAdditional borontribromide (4 mL) was added at room temperature over a period of 2 min.
  2. stirringthe reaction was stirred for 3 h
  3. concentrationThe reaction mixture was concentrated
  4. waitkept on the high vacuum pump for 10 min
  5. additionDichloromethane (5 mL) was added
  6. customfollowed by 3 mL of borontribromide at room temperature
  7. stirringThe contents were stirred at room temperature for 60 h
  8. temperatureThe reaction mixture was cooled to 0° C.
  9. customquenched by the slow addition of methanol (˜0 mL)
  10. stirringThe contents were stirred for 10 min.
  11. concentrationconcentrated under reduced pressure
  12. customThe resulting residue was partitioned between dichloromethane (25 mL) and water (10 mL)
  13. washThe dichloromethane layer was washed with brine (20 mL)
  14. dry with materialdried over sodium sulfate
  15. concentrationconcentrated
  16. customThe resulting solid was triturated with ethyl acetate (5 mL)
  17. filtrationcollected by filtration
  18. washwashed with ethyl acetate (2×3 mL)
  19. customdried

Sources & evidence

ORD record
ord-2774511dff024d499085fac95d4199d3
Source dataset
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09216972B2

Reaction notes

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