Potassium Carbonate → 2-((2-(2,4-Difluorophenyl)oxiran-2-yl)difluoromethyl)-5-(2,2,2-trifluoroethoxy)pyridine

HRID 63259Notes

Reaction equation

HRID 63259 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1([C:12]([F:21])([F:20])[C:13]2[N:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)[CH2:11][O:10]1.C([O-])([O-])=O.[K+].[K+].FC(F)(F)S(O[CH2:34][C:35]([F:38])([F:37])[F:36])(=O)=O>CC(C)=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1([C:12]([F:20])([F:21])[C:13]2[CH:14]=[CH:15][C:16]([O:19][CH2:34][C:35]([F:38])([F:37])[F:36])=[CH:17][N:18]=2)[CH2:11][O:10]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 866755046-((2-(2,4-Difluorophenyl)oxiran-2-yl) difluoromethyl)pyridin-3-ol

Product 1

HCID 1177204332-((2-(2,4-Difluorophenyl)oxiran-2-yl)difluoromethyl)-5-(2,2,2-trifluoroethoxy)pyridine

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
25 °C

Procedure

To a magnetically stirred mixture of 6-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridin-3-ol (600 mg, 2.005 mmol) and K2CO3 (305 mg, 2.206 mmol) in acetone (6.76 mL) was added 2,2,2-trifluoroethyl trifluoromethanesulfonate (558 mg, 2.406 mmol) in a 20 mL vial under an atmosphere of air. The reaction mixture was stirred at 25° C. for 16 h. As the reaction progressed the reaction mixture became a cloudy beige suspension. The reaction was quenched with MeOH (2 mL) and then volatiles were removed under a gentle stream of N2. The resulting residue was partitioned with water and CH2Cl2 and the organic layer was removed. The aqueous layer was washed CH2Cl2 (2×) and combined organic layers were dried by passing through a phase separator. Volatiles were removed under a gentle stream of N2 and the crude orange oil was carried on without further purification (779 mg, 97%): 1H NMR (400 MHz, CDCl3) δ 8.40 (d, J=2.9 Hz, 1H), 7.46 (d, J=8.7 Hz, 1H), 7.38 (dd, J=14.7, 8.2 Hz, 1H), 7.28 (d, J=2.9 Hz, 1H), 6.88-6.80 (m, 1H), 6.78-6.71 (m, 1H), 4.44 (q, J=7.9 Hz, 2H), 3.43 (d, J=5.1 Hz, 1H), 3.00-2.95 (m, 1H); 19F NMR (376 MHz, CDCl3) δ −73.75 (s, 3F), −107.01 (dd, J=257.0, 8.5 Hz, 1F), −107.55-−108.43 (m, 2F), −109.41 (q, J=8.5 Hz, 1F). ESIMS m/z 382 ([M+H]+).

Workup

  1. customThe reaction was quenched with MeOH (2 mL)
  2. customvolatiles were removed under a gentle stream of N2
  3. customThe resulting residue was partitioned with water and CH2Cl2
  4. customthe organic layer was removed
  5. washThe aqueous layer was washed CH2Cl2 (2×)
  6. customwere dried
  7. customVolatiles were removed under a gentle stream of N2
  8. customthe crude orange oil was carried on without further purification (779 mg, 97%)

Sources & evidence

ORD record
ord-7ea6cee5f3424b6fb98a34f4aec33926
Source dataset
uspto-grants-2016_09
Patent number
US09447073B2

Reaction notes

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