Potassium vinyltrifluoroborate → methyl 4-(4-(difluoromethyl)-5-vinylthiazol-2-yl)-1-methyl-1H-pyrazole-5-carboxylate

HRID 874425

Reaction equation

HRID 874425 reaction equation
F[C:2](OB([O-])[O-])=[C:3]([F:5])[F:4].[K+].[K+].Br[C:13]1[S:17][C:16]([C:18]2[CH:19]=[N:20][N:21]([CH3:27])[C:22]=2[C:23]([O:25][CH3:26])=[O:24])=[N:15][C:14]=1[CH:28](F)F.[B-](F)(F)(F)C=C.[K+]>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(OCC)(=O)C.C(N(CC)CC)C.C(O)C>[F:4][CH:3]([F:5])[C:2]1[N:15]=[C:16]([C:18]2[CH:19]=[N:20][N:21]([CH3:27])[C:22]=2[C:23]([O:25][CH3:26])=[O:24])[S:17][C:13]=1[CH:14]=[CH2:28]

Participants

8

Reactant 3

HCID 23679353Potassium vinyltrifluoroborateHCID 86620274Potassium trifluorovinylborateHCID 90383233methyl 4-(5-bromo-4-(difluoromethyl)thiazol-2-yl)-1-methyl-1H-pyrazole-5-carboxylate

Product 1

HCID 117761094methyl 4-(4-(difluoromethyl)-5-vinylthiazol-2-yl)-1-methyl-1H-pyrazole-5-carboxylateYield 58%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 702EthanolSolventHCID 8471TriethylamineSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Potassium trifluorovinylborate (172 mg), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride (31 mg), and triethylamine (59.4 μl) were added to an ethanol (2.1 ml) solution of the methyl 4-(5-bromo-4-(difluoromethyl)thiazol-2-yl)-1-methyl-1H-pyrazole-5-carboxylate (150 mg) obtained in (Example 1.4) <Step 1>, and the obtained mixture was then stirred in a nitrogen atmosphere at 100° C. for 17 hours. Thereafter, potassium trifluoro(vinyl)borate (342 mg), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride (62 mg), and triethylamine (59.4 μl) were added to the reaction solution, and the obtained mixture was stirred again in a nitrogen atmosphere at 100° C. for 2 hours 40 minutes. Thereafter, ethyl acetate (100 ml) and a saturated saline (50 ml) were added to the reaction solution. An organic layer was extracted, 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=95:5-50:50), so as to obtain the title compound (74 mg) in the form of a colorless solid.

Workup

  1. customobtained in (Example 1.4) <Step 1>
  2. stirringthe obtained mixture was stirred again in a nitrogen atmosphere at 100° C. for 2 hours 40 minutes
  3. extractionAn organic layer was extracted
  4. dry with materialwas then dried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled away under reduced pressure
  6. customthe obtained residue was then purified by silica gel column chromatography (silica gel: eluent; heptane:ethyl acetate=95:5-50:50)

Sources & evidence

ORD record
ord-5246daefc1cc49a5a4b2813555964569
Source dataset
uspto-grants-2015_03
Patent number
US08980889B2

Linked notes

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