N,N-Dimethylglycine → 4-[3-(trifluoromethyl)-4,5,6,7-tetrahydroindazol-1-yl]benzoic acid

HRID 230617Notes

Reaction equation

[F:1][C:2]([F:13])([F:12])[C:3]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[NH:5][N:4]=1.I[C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=[O:20])=[CH:17][CH:16]=1.CN(C)CC(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[F:13][C:2]([F:1])([F:12])[C:3]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[N:5]([C:15]2[CH:23]=[CH:22][C:18]([C:19]([OH:21])=[O:20])=[CH:17][CH:16]=2)[N:4]=1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole (950 mg, 5.0 mmol), 4-iodobenzoic acid (1.24 g, 5.0 mmol), N,N-dimethylglycine (20 mol %, 103 mg, 1.0 mmol), copper (I) iodide (10 mol %, 95 mg, 0.5 mmol) and potassium carbonate (1.45 g, 10.5 mmol) in dimethylsulfoxide (15 ml) was stirred at 130° C. in an oil bath under argon for 3.25 hours. The reaction mix was then filtered under vacuum and the filtrate separated between ethyl acetate and water. The aqueous layer was retained and acidified to approximately Ph2 using 5M aqueous HCl. The aqueous fraction was then washed 3 times with ethyl acetate. The organic layers were combined and dried over sodium sulphate, and the solvent was removed by rotary evaporation to give the title compound as a brown solid (1.62 g, 100%).

Workup

additionThe reaction mix
filtrationwas then filtered under vacuum
customthe filtrate separated between ethyl acetate and water
washThe aqueous fraction was then washed 3 times with ethyl acetate
dry with materialdried over sodium sulphate
customthe solvent was removed by rotary evaporation

Sources & evidence

ORD record: ord-4e63b2fd1a7c44fbb58d51d7ca002051
Source dataset: uspto-grants-2009_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07566735B2

Reaction notes

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