Water → 2-Difluoromethoxy-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-benzonitrile

HRID 1172692Notes

Reaction equation

HRID 1172692 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[S:5][C:6]=1[CH:7]([OH:10])[CH2:8][CH3:9].[H-].[Na+].[F:23][CH:24]([F:35])[O:25][C:26]1[CH:33]=[C:32](F)[CH:31]=[CH:30][C:27]=1[C:28]#[N:29].O>CN(C)C=O>[F:23][CH:24]([F:35])[O:25][C:26]1[CH:33]=[C:32]([O:10][CH:7]([C:6]2[S:5][C:4]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:18])[F:19])=[CH:13][CH:12]=3)=[N:3][C:2]=2[CH3:1])[CH2:8][CH3:9])[CH:31]=[CH:30][C:27]=1[C:28]#[N:29]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 235491291-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propan-1-olHCID 59295388HCID 59295388, compound

Product 1

HCID 595563432-Difluoromethoxy-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-benzonitrileYield 43.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
5 °C

Procedure

To a solution of 1.7 g of 1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propan-1-ol in 4.7 mL of dimethylformamide at 5° C. was added 250 mg of a 55% suspension of sodium hydride in mineral oil. The reaction volume was completed with dimethylformamide to about 8.5 mL. The reaction mixture was stirred for 30 minutes at 5° C. 4.3 mL of the resulting mixture was slowly added to a solution of 450 mg of 2-difluoromethoxy-4-fluoro-benzonitrile in 2 mL of dimethylformamide at 5° C. The resulting mixture was stirred at 5° C. allowing the temperature to warm up to room temperature. It was then heated in a sealed tube to 60° C. under microwave irradiation for 15 minutes. After allowing it to cool down to room temperature, the mixture was poured into water and extracted with dichloromethane. The organic extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (gradient from heptane 100 to heptane 50/ethyl acetate 50) to give 490 mg of 2-difluoromethoxy-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-benzonitrile.

Workup

  1. stirringThe resulting mixture was stirred at 5° C.
  2. temperatureto warm up to room temperature
  3. temperatureIt was then heated in a sealed tube to 60° C. under microwave irradiation for 15 minutes
  4. temperatureto cool down to room temperature
  5. extractionextracted with dichloromethane
  6. dry with materialThe organic extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by column chromatography on silica gel (gradient from heptane 100 to heptane 50/ethyl acetate 50)

Sources & evidence

ORD record
ord-5aec2aa838204ffcae4d358ec8e1b94b
Source dataset
uspto-grants-2010_11
Patent number
US07834030B2

Reaction notes

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