Potassium Carbonate → HCID 71476160, compound

HRID 1507010Notes

Reaction equation

HRID 1507010 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:32])([F:31])[C:13]2[N:18]=[CH:17][C:16]([CH:19]([C:21]3[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=3)[OH:20])=[CH:15][CH:14]=2)[CH2:11][O:10]1.[NH:33]1[CH:37]=[N:36][N:35]=[N:34]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:10])([CH2:11][N:33]1[CH:37]=[N:36][N:35]=[N:34]1)[C:12]([F:31])([F:32])[C:13]1[CH:14]=[CH:15][C:16]([CH:19]([OH:20])[C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:28])([F:30])[F:29])=[CH:23][CH:22]=2)=[CH:17][N:18]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 86675445HCID 86675445, compoundHCID 178418441HCID 178418441, compound

Product 1

HCID 71476160HCID 71476160, compoundYield 178.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

To a stirred solution of (6-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridin-3-yl)(4-(trifluoromethyl)phenyl)methanol (AM; 600 mg, 0.32 mmol) in dry DMF (10 mL) was added 1H-tetrazole (138 mg, 1.97 mmol) followed by K2CO3 (181 mg, 1.31 mmol) at RT under inert atmosphere. The resulting reaction mixture was gradually heated up to 65° C. and stirred for 16 h; progress of the reaction was monitored by TLC. The reaction mixture was cooled to RT, diluted with ice-cold water (50 mL) and extracted with EtOAc (3×50 mL). The combined organic extracts were washed with water (50 mL) and brine (50 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain the crude material. Purification by silica gel column chromatography (eluting with 35-40% EtOAc/hexanes) afforded 72 (diastereomeric mixture; 300 mg, 0.57 mmol, 43%) as an off-white solid. 1H NMR (500 MHz, CDCl3; mixture of diastereomers): δ 8.73 (s, 2H), 8.54 (s, 1H), 8.48 (s, 1H), 7.83 (d, J=8.0 Hz, 1H), 7.79 (d, J=8.0 Hz, 1H), 7.64 (d, J=8.0 Hz, 4H), 7.62-7.58 (m, 4H), 7.50-7.44 (m, 4H), 7.42-7.39 (m, 2H), 6.81-6.74 (m, 2H), 6.72-6.64 (m, 2H), 5.99-5.93 (m, 2H), 5.48-5.40 (m, 2H), 5.20-5.12 (m, 2H), 2.78 (s, 1H), 2.70 (s, 1H). MS (ESI): m/z 528 [M+H]+.

Workup

  1. customThe resulting reaction mixture
  2. temperatureThe reaction mixture was cooled to RT
  3. extractionextracted with EtOAc (3×50 mL)
  4. washThe combined organic extracts were washed with water (50 mL) and brine (50 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto obtain the crude material
  8. customPurification
  9. washby silica gel column chromatography (eluting with 35-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d3bbb463c39d42f18a5850034b137844
Source dataset
uspto-grants-2015_12
Patent number
US09221791B2

Reaction notes

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