Water → 5-Fluoro-2-(2,2,2-trifluoro-ethoxy)-4-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-ylmethoxy]-benzonitrile

HRID 2263436Notes

Reaction equation

HRID 2263436 reaction equation
[CH2:1]([OH:6])[C:2]([F:5])([F:4])[F:3].CC(C)([O-])C.[K+].F[C:14]1[CH:21]=[C:20]([O:22][CH2:23][C:24]2[S:28][C:27]([C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=3)=[N:26][C:25]=2[CH2:39][N:40]2[CH2:45][CH2:44][CH:43]([C:46]([F:49])([F:48])[F:47])[CH2:42][CH2:41]2)[C:19]([F:50])=[CH:18][C:15]=1[C:16]#[N:17].O>O1CCCC1.C(O)(C)(C)C>[F:50][C:19]1[C:20]([O:22][CH2:23][C:24]2[S:28][C:27]([C:29]3[CH:30]=[CH:31][C:32]([C:35]([F:37])([F:38])[F:36])=[CH:33][CH:34]=3)=[N:26][C:25]=2[CH2:39][N:40]2[CH2:45][CH2:44][CH:43]([C:46]([F:49])([F:47])[F:48])[CH2:42][CH2:41]2)=[CH:21][C:14]([O:6][CH2:1][C:2]([F:5])([F:4])[F:3])=[C:15]([CH:18]=1)[C:16]#[N:17]

Participants

7

Reactant 4

HCID 962WaterHCID 64092,2,2-TrifluoroethanolHCID 23665647Potassium tert-butoxideHCID 595947472,5-Difluoro-4-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-ylmethoxy]-benzonitrile

Product 1

HCID 595947455-Fluoro-2-(2,2,2-trifluoro-ethoxy)-4-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-ylmethoxy]-benzonitrileYield 40.3%

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of 190 mg of trifluoroethanol in 1.16 mL of tetrahydrofuran at 5° C. was slowly added 2.2 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 890 mg of 2,5-difluoro-4-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-ylmethoxy]-benzonitrile in 3.1 mL of tetrahydrofuran at −60° C. The resulting mixture was 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 triturated with diisopropyl ether and filtered to give 410 mg of 5-fluoro-2-(2,2,2-trifluoro-ethoxy)-4-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-ylmethoxy]-benzonitrile as a white solid.

Workup

  1. customat 5° C.
  2. stirringThe resulting mixture was stirred overnight
  3. temperatureto warm up to room temperature
  4. extractionextracted with dichloromethane
  5. dry with materialThe organic extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was triturated with diisopropyl ether
  9. filtrationfiltered

Sources & evidence

ORD record
ord-016e41913caf42dc9ffb1aebb5fd0935
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

Loading…