Water → HCID 59594780, compound

HRID 2263432Notes

Reaction equation

HRID 2263432 reaction equation
[F:1][C:2]([F:28])([F:27])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:10][C:11]([CH2:25][OH:26])=[C:12]([CH2:14][N:15]3[CH2:20][CH2:19][CH:18]([C:21]([F:24])([F:23])[F:22])[CH2:17][CH2:16]3)[N:13]=2)=[CH:5][CH:4]=1.[H-].[Na+].[F:31][CH:32]([F:43])[O:33][C:34]1[CH:41]=[C:40](F)[CH:39]=[CH:38][C:35]=1[C:36]#[N:37].O>CN(C)C=O>[F:31][CH:32]([F:43])[O:33][C:34]1[CH:41]=[C:40]([O:26][CH2:25][C:11]2[S:10][C:9]([C:6]3[CH:7]=[CH:8][C:3]([C:2]([F:1])([F:27])[F:28])=[CH:4][CH:5]=3)=[N:13][C:12]=2[CH2:14][N:15]2[CH2:20][CH2:19][CH:18]([C:21]([F:22])([F:24])[F:23])[CH2:17][CH2:16]2)[CH:39]=[CH:38][C:35]=1[C:36]#[N:37]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 592953882-(Difluoromethoxy)-4-fluorobenzonitrileHCID 59556321HCID 59556321, compound

Product 1

HCID 59594780HCID 59594780, compoundYield 82.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of 3 g of [2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-yl]-methanol in 12 mL of dimethylformamide at 5° C. was added 319 mg of a 55% suspension of sodium hydride in mineral oil. The resulting mixture was stirred for 30 minutes at 5° C. 4.7 mL of the resulting solution was slowly added to a solution 319 mg of 2-difluoromethoxy-4-fluoro-benzonitrile in 1.2 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 0.83 g of 2-difluoromethoxy-4-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-ylmethoxy]-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-f364c0489f4449c3a7a5e7d633433fb4
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

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