Trifluoromethanesulfonic anhydride → HCID 86669914, compound

HRID 1506456Notes

Reaction equation

HRID 1506456 reaction equation
FC(F)(F)S([O:6][S:7]([C:10]([F:13])([F:12])[F:11])(=[O:9])=[O:8])(=O)=O.[F:16][C:17]1([F:46])[C:44]2[C:39](=[CH:40][CH:41]=[C:42](O)[CH:43]=2)[C:20]2=[N:21][O:22][C:23]([C:24]3[C:28]([C:29]([F:32])([F:31])[F:30])=[C:27]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[O:26][N:25]=3)=[C:19]2[CH2:18]1>N1C=CC=CC=1>[F:13][C:10]([F:11])([F:12])[S:7]([O:6][C:42]1[CH:43]=[C:44]2[C:39](=[CH:40][CH:41]=1)[C:20]1=[N:21][O:22][C:23]([C:24]3[C:28]([C:29]([F:31])([F:30])[F:32])=[C:27]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[O:26][N:25]=3)=[C:19]1[CH2:18][C:17]2([F:46])[F:16])(=[O:8])=[O:9]

Participants

4

Reactant 2

HCID 67749Trifluoromethanesulfonic anhydrideHCID 136349532HCID 136349532, compound

Product 1

HCID 86669914HCID 86669914, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

Trifluoromethanesulfonic anhydride (0.012 mL, 0.069 mmol) was added to a solution of 5,5-difluoro-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-ol (Preparation 66D, 0.020 g, 0.046 mmol) in pyridine (5.0 mL) at 0° C. over a period of 5 min. The reaction mixture was stirred at 0° C. for ten minutes, warmed to room temperature, and stirred overnight. The reaction mixture was concentrated, and the yellowish-brown residue was partitioned between ethyl acetate (10 mL) and water (10 mL). The ethyl acetate layer was collected, washed with 1N aqueous Hydrochloric acid (10 mL), saturated aqueous solution of sodium bicarbonate (10 mL), brine (10 mL), and dried over sodium sulfate. Concentration followed by purification by silica gel chromatography eluting with a mixture of ethyl acetate and hexane (10%-20%) afforded 5,5-difluoro-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl trifluoromethanesulfonate (0.024 g, 0.042 mmol, 92% yield) as a viscous liquid. The product had an HPLC ret. time=3.34 min. (condition B). LC/MS M+1=566.3, 568.4.

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred overnight
  3. concentrationThe reaction mixture was concentrated
  4. customthe yellowish-brown residue was partitioned between ethyl acetate (10 mL) and water (10 mL)
  5. customThe ethyl acetate layer was collected
  6. washwashed with 1N aqueous Hydrochloric acid (10 mL), saturated aqueous solution of sodium bicarbonate (10 mL), brine (10 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationConcentration
  9. customfollowed by purification by silica gel chromatography
  10. washeluting with a mixture of ethyl acetate and hexane (10%-20%)

Sources & evidence

ORD record
ord-3b5916ced17e41c68b29507a54024fb3
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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