Potassium Phosphate, Tribasic → tert-butyl 4-(2-fluoro-4-hydroxy-5-methoxyphenyl)-1H-pyrazole-1-carboxylate

HRID 1027258Notes

Reaction equation

HRID 1027258 reaction equation
Br[C:2]1[C:7]([F:8])=[CH:6][C:5]([OH:9])=[C:4]([O:10][CH3:11])[CH:3]=1.CC1(C)C(C)(C)OB([C:20]2[CH:21]=[N:22][N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH:24]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C>[F:8][C:7]1[CH:6]=[C:5]([OH:9])[C:4]([O:10][CH3:11])=[CH:3][C:2]=1[C:20]1[CH:21]=[N:22][N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH:24]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 265965254-Bromo-5-fluoro-2-methoxyphenol

Product 1

HCID 86710669tert-butyl 4-(2-fluoro-4-hydroxy-5-methoxyphenyl)-1H-pyrazole-1-carboxylateYield 100.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a reaction flask was added 4-bromo-5-fluoro-2-methoxyphenol (500 mg, 2.26 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (998 mg, 3.39 mmol), potassium phosphate (1.4 g, 6.79 mmol), and XPhosPalladacycle (178 mg, 0.23 mmol), followed by addition of DMF (11 mL). The vial was purged with N2 for 5 minutes and the reaction mixture was heated at 50° C. in the microwave for 16 h. The reaction mixture was concentrated in vacuo and the crude product was purified by silica gel to afford tert-butyl 4-(2-fluoro-4-hydroxy-5-methoxyphenyl)-1H-pyrazole-1-carboxylate (700 mg) MS [M+H+]=307.5.

Workup

  1. customThe vial was purged with N2 for 5 minutes
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe crude product was purified by silica gel

Sources & evidence

ORD record
ord-229991ff62b14864b61c73cf625fdc28
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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