Tricyclohexylphosphine → 2-Cyclopropyl-4-{2,2,2-trifluoro-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxymethyl}-benzonitrile

HRID 1172687Notes

Reaction equation

HRID 1172687 reaction equation
Br[C:2]1[CH:9]=[C:8]([CH2:10][O:11][CH:12]([C:17]2[S:21][C:20]([C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=3)=[N:19][C:18]=2[CH3:32])[C:13]([F:16])([F:15])[F:14])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C1(P([CH:46]2[CH2:51][CH2:50]CCC2)C2CCCCC2)CCCCC1.C1(B(O)O)CC1.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[CH:50]1([C:2]2[CH:9]=[C:8]([CH2:10][O:11][CH:12]([C:17]3[S:21][C:20]([C:22]4[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=4)=[N:19][C:18]=3[CH3:32])[C:13]([F:16])([F:15])[F:14])[CH:7]=[CH:6][C:3]=2[C:4]#[N:5])[CH2:51][CH2:46]1

Participants

8

Reactant 4

HCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 595563762-Bromo-4-{2,2,2-trifluoro-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxymethyl}-benzonitrile

Product 1

HCID 595563322-Cyclopropyl-4-{2,2,2-trifluoro-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxymethyl}-benzonitrileYield 365.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
10 °C

Procedure

147 mg 2-Bromo-4-{2,2,2-trifluoro-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxymethyl}-benzonitrile, 15 mg Tricyclohexylphosphine, 71 mg Cyclopropylboronic acid and 224 mg Tripotassiumphosphate monohydrate were dissolved in a mixture of 2 ml toluene and 0.2 ml water. The reaction mixture was degassed and 62 mg palladium(II) acetate were added and the reaction mixture heated under microwave irradiation at 10° C. for 2.5 hours. The cooled reaction mixture was diluted by addition of 50 ml ethyl acetate and filtered. The filtrate was evaporated and the residue purified by reverse phase HPLC to obtain 97 mg 2-Cyclopropyl-4-{2,2,2-trifluoro-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxymethyl}-benzonitrile as an oil.

Workup

  1. customThe reaction mixture was degassed
  2. addition62 mg palladium(II) acetate were added
  3. customThe cooled reaction mixture
  4. filtrationfiltered
  5. customThe filtrate was evaporated
  6. customthe residue purified by reverse phase HPLC

Sources & evidence

ORD record
ord-10bb620c473547968ea0bd0bd254c052
Source dataset
uspto-grants-2010_11
Patent number
US07834030B2

Reaction notes

Loading…