Potassium Phosphate, Tribasic → 6-(4-Hydroxy-2-methyl-phenyl)-1-methyl-1H-indazole-3-carboxylic Acid

HRID 424816Notes

Reaction equation

C[O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10](Br)=[CH:11][CH:12]=2)[N:7]([CH3:15])[N:6]=1)=[O:4].CC1(C)C(C)(C)OB([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[OH:30])O1.[CH:32]1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:30][C:25]1[CH:24]=[CH:29][C:28]([C:10]2[CH:9]=[C:8]3[C:13]([C:5]([C:3]([OH:2])=[O:4])=[N:6][N:7]3[CH3:15])=[CH:12][CH:11]=2)=[C:27]([CH3:32])[CH:26]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a degassed solution of 6-bromo-1-methyl-1H-indazole-3-carboxylic acid methyl ester (0.61 g, 2.4 mmol), 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl-phenol (0.84, 3.6 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (0.098 g, 0.240 mmol), and potassium phosphate (1.0 g, 4.8 mmol) in dioxane (10 mL) and water (5 mL) is degassed and treated with Pd(OAc)2 (27 mg, 0.12 mmol). The reaction is degassed again and heated to 90° C. for 18 h. The reaction is cooled to room temperature, concentrated onto silica gel under reduced pressure, and purified via flash chromatography using a gradient of 10% to 30% EtOAc in Hexanes to yield the title compound (0.53 g, 75%). ES/MS m/e 297.0 (M+1).

Workup

customThe reaction is degassed again
temperatureThe reaction is cooled to room temperature
concentrationconcentrated onto silica gel under reduced pressure
custompurified via flash chromatography

Sources & evidence

ORD record: ord-4bef447f611f48f3ad5cbdf1b92d3692
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08106077B2

Reaction notes

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