Tricyclohexylphosphine → methyl 4-(5-cyclopropyl-4-(difluoromethyl)thiazol-2-yl)-1-methyl-1H-pyrazole-5-carboxylate

HRID 874426Notes

Reaction equation

HRID 874426 reaction equation
[CH:1]1(B(O)O)[CH2:3][CH2:2]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.Br[C:27]1[S:31][C:30]([C:32]2[CH:33]=[N:34][N:35]([CH3:41])[C:36]=2[C:37]([O:39][CH3:40])=[O:38])=[N:29][C:28]=1[CH:42]([F:44])[F:43].C(=O)([O-])O.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.C1(C)C=CC=CC=1.O>[CH:1]1([C:27]2[S:31][C:30]([C:32]3[CH:33]=[N:34][N:35]([CH3:41])[C:36]=3[C:37]([O:39][CH3:40])=[O:38])=[N:29][C:28]=2[CH:42]([F:43])[F:44])[CH2:3][CH2:2]1

Participants

9

Reactant 4

HCID 75806TricyclohexylphosphineHCID 516892Sodium BicarbonateHCID 2760897Cyclopropylboronic acidHCID 90383233methyl 4-(5-bromo-4-(difluoromethyl)thiazol-2-yl)-1-methyl-1H-pyrazole-5-carboxylate

Product 1

HCID 90383509methyl 4-(5-cyclopropyl-4-(difluoromethyl)thiazol-2-yl)-1-methyl-1H-pyrazole-5-carboxylateYield 83%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Cyclopropylboronic acid (61 mg), palladium acetate (11 mg), phosphoric acid potassium salts (203 mg), water (0.53 ml), and tricyclohexylphosphine (27 mg) were added to a toluene (6 ml) solution of the methyl 4-(5-bromo-4-(difluoromethyl)thiazol-2-yl)-1-methyl-1H-pyrazole-5-carboxylate (84 mg) obtained in (Example 1.4) <Step 1>, and the obtained mixture was then stirred in a nitrogen atmosphere at 100° C. for 1.5 hours. Thereafter, ethyl acetate (50 ml) and a saturated sodium hydrogen carbonate aqueous solution (30 ml) were added to the reaction solution. After extraction of organic layers, water layers were extracted with ethyl acetate (50 ml). The organic layers were combined. The combined organic layer was washed with a saturated saline, and was then dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, and the obtained residue was then purified by silica gel column chromatography (silica gel: eluent; heptane:ethyl acetate=93:7-40:60), so as to obtain the title compound (62 mg) in the form of a light brown solid.

Workup

  1. customobtained in (Example 1.4) <Step 1>
  2. extractionAfter extraction of organic layers, water layers
  3. extractionwere extracted with ethyl acetate (50 ml)
  4. washThe combined organic layer was washed with a saturated saline
  5. dry with materialwas then dried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled away under reduced pressure
  7. customthe obtained residue was then purified by silica gel column chromatography (silica gel: eluent; heptane:ethyl acetate=93:7-40:60)

Sources & evidence

ORD record
ord-4741a064b7104e719f66cab5770e236b
Source dataset
uspto-grants-2015_03
Patent number
US08980889B2

Reaction notes

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