Water → HCID 59556309, compound

HRID 1172697Notes

Reaction equation

HRID 1172697 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].CC(C)([O-])C.[K+].[F:27][C:28]1[CH:35]=[C:34](F)[C:33]([F:37])=[CH:32][C:29]=1[C:30]#[N:31].O>O1CCCC1.C(O)(C)(C)C>[F:27][C:28]1[CH:35]=[C:34]([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])[C:33]([F:37])=[CH:32][C:29]=1[C:30]#[N:31]

Participants

7

Reactant 4

HCID 962WaterHCID 5938132,4,5-TrifluorobenzonitrileHCID 235491291-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propan-1-olHCID 23665647Potassium tert-butoxide

Product 1

HCID 59556309HCID 59556309, compoundYield 95.5%

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of 900 mg of 1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propan-1-ol in 2 mL of tetrahydrofuran at 5° C. was slowly added 3.3 mL of a molar solution of potassium tert-butoxide in tert-butanol. After stirring at 5° C. for 30 minutes, the resulting solution was slowly added to a solution of 469 mg of 2,4,5-trifluoro-benzonitrile in 2 mL of tetrahydrofuran at −60° C. The resulting mixture was stirred for 1 h at −60° C. then stirred overnight allowing the temperature to warm up to room temperature. It was then 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 80/ethyl acetate 20) to give 1.25 g of 2,5-difluoro-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-benzonitrile.

Workup

  1. customat 5° C.
  2. stirringThe resulting mixture was stirred for 1 h at −60° C.
  3. stirringthen stirred overnight
  4. temperatureto warm up 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 80/ethyl acetate 20)

Sources & evidence

ORD record
ord-640d9a37120e4412a9ff258c71214264
Source dataset
uspto-grants-2010_11
Patent number
US07834030B2

Reaction notes

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