Potassium Carbonate → HCID 71143764, compound

HRID 1396227Notes

Reaction equation

HRID 1396227 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:30])([F:29])[C:13]2[N:18]=[CH:17][C:16]([CH2:19][O:20][C:21]3[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][N:22]=3)=[CH:15][CH:14]=2)[CH2:11][O:10]1.[NH:31]1[CH:35]=[N:34][N:33]=[N:32]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOCC>[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:31]1[CH:35]=[N:34][N:33]=[N:32]1)[C:12]([C:13]1[N:18]=[CH:17][C:16]([CH2:19][O:20][C:21]2[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][N:22]=2)=[CH:15][CH:14]=1)([F:29])[F:30]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 89310140HCID 89310140, compoundHCID 178418441HCID 178418441, compound

Product 1

HCID 71143764HCID 71143764, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

To a magnetically stirred mixture of 6-((6-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridin-3-yl)methoxy)nicotinonitrile (BZ; 200 mg, 0.482 mmol) and 1H-tetrazole (67.5 mg, 0.963 mmol) in dry DMF (4.815 mL) was added K2CO3 (133 mg, 0.963 mmol) in a dry 25 mL vial under N2 atmosphere. The reaction mixture was stirred at 55° C. for 36 hours, then cooled to RT, and diluted with ice-water and ether. The layers were separated and the aq. layer was extracted again with ether (2×). The combined ether extracts were dried over sodium sulfate, filtered, and evaporated. The crude residue was purified on silica (40 gram column, gradient over 15 min to 40% EA/Hex, hold 10 min then 10 min at 80% EA/hex, monitor 240 and 254 nm). The respective product fractions were evaporated to afford the title compound contaminated with DMF. The material was diluted with water and extracted 3× with ether, the combined ether extracts were diluted with pet. ether and washed with sat'd NH4Cl (2×) and brine (1×), dried over MgSO4, filtered, and evaporated to afford 98. Yield=62 mg (25.2%) of a white foam. 1H NMR (400 MHz, CDCl3) δ 8.75 (s, 1H), 8.63 (d, J=1.3 Hz, 1H), 8.48 (dd, J=2.3, 0.8 Hz, 1H), 7.91 (dd, J=8.2, 2.1 Hz, 1H), 7.85 (dd, J=8.7, 2.4 Hz, 1H), 7.62 (d, J=8.0 Hz, 1H), 7.56 (s, 1H), 7.35 (td, J=9.0, 6.5 Hz, 1H), 6.92 (dd, J=8.5, 0.8 Hz, 1H), 6.76 (ddd, J=12.0, 8.5, 2.5 Hz, 1H), 6.71-6.61 (m, 1H), 5.56 (d, J=14.3 Hz, 1H), 5.50 (s, 2H), 5.13 (dd, J=14.2, 1.1 Hz, 1H). 1H-decoupled 19F NMR (376 MHz, CDCl3) δ −103.83 (ddd, J=42.2, 17.0, 10.2 Hz), −104.20 (d, J=16.3 Hz), −104.89 (d, J=16.3 Hz), −107.90-108.07 (m), −110.92 (dd, J=262.9, 42.2 Hz). MS (ESI): m/z 486.1 (M+H)+.

Workup

  1. temperaturecooled to RT
  2. customThe layers were separated
  3. extractionthe aq. layer was extracted again with ether (2×)
  4. dry with materialThe combined ether extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude residue was purified on silica (40 gram column, gradient over 15 min to 40% EA/Hex
  8. waithold 10 min
  9. custom10 min
  10. customThe respective product fractions were evaporated

Sources & evidence

ORD record
ord-441ccdbdecca46c0976830ab00cb2b52
Source dataset
uspto-grants-2014_12
Patent number
US08901121B2

Reaction notes

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