Potassium Carbonate → 2-amino-5-(1-methyl-1H-pyrazol-4-yl)-4-trifluoromethyl-benzoic acid methyl ester

HRID 1441576Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8](I)[C:7]([C:11]([F:14])([F:13])[F:12])=[CH:6][C:5]=1[NH2:15].[CH3:17][N:18]1[CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[N:19]1.C([O-])([O-])=O.[K+].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([C:21]2[CH:20]=[N:19][N:18]([CH3:17])[CH:22]=2)[C:7]([C:11]([F:14])([F:13])[F:12])=[CH:6][C:5]=1[NH2:15]

Participants

Conditions

Temperature: 90 °C

Procedure

2-Amino-5-iodo-4-trifluoromethyl-benzoic acid methyl ester (300 mg, 0.87 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)1H-pyrazole (181 mg, 1.0 equiv), K2CO3 (303 mg, 2.5 equiv.) and triphenylphosphine (45 mg. 0.2 equiv) were weighed in air and added in a flame-dried flask. Bis(dibenzylidenacetone)palladium (25 mg, 0.05 equiv) was added and the flask was closed by a septum. Dioxane (6 mL) was added and the mixture was stirred for 18 h (TLC control) at 90° C. The catalyst was filtered off and washed with EtOAc, the filtrate was evaporated to dryness. The crude product was purified by column chromatography (silica gel 60, EtOAc/hexanes 1/3 to 1/2) to give 2-amino-5-(1-methyl-1H-pyrazol-4-yl)-4-trifluoromethyl-benzoic acid methyl ester (0.57 mmol, 66%) as a white solid. ESI-MS: m/z 300 [M+H]+, rt: 4.97 min.

Workup

additionadded in a flame-dried flask
customthe flask was closed by a septum
filtrationThe catalyst was filtered off
washwashed with EtOAc
customthe filtrate was evaporated to dryness
customThe crude product was purified by column chromatography (silica gel 60, EtOAc/hexanes 1/3 to 1/2)

Sources & evidence

ORD record: ord-fda103d9cabc413e8f32fc46674c5616
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07655666B2

Reaction notes

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