N,N-Dimethylglycine → {4-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]phenyl}methanol

HRID 1988665Notes

Reaction equation

I[C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][CH:3]=1.[F:10][C:11]([F:22])([F:21])[C:12]1[C:20]2[CH2:19][CH2:18][CH2:17][CH2:16][C:15]=2[NH:14][N:13]=1.CN(C)CC(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[F:22][C:11]([F:10])([F:21])[C:12]1[C:20]2[CH2:19][CH2:18][CH2:17][CH2:16][C:15]=2[N:14]([C:2]2[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][CH:3]=2)[N:13]=1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of 4-iodobenzylalcohol (1.23 g, 5.25 mmol), 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole (950 mg, 5 mmol), copper (I) iodide (10 mol %, 95 mg, 0.5 mmol), N,N-dimethylglycine (20 mol %, 103 mg, 1 mmol) and potassium carbonate (1.45 g, 10.5 mmol) in dimethylsulfoxide (30 ml) was stirred at 130° C. in an oil bath for 23 h. The reaction mix was cooled and partitioned between dichloromethane (30 ml) and brine (150 ml). The organic layer was removed filtered and the solvent removed under reduced pressure. The resulting product was purified by flash column chromatography on a Biotage 40+M column eluting from 0-60% ethyl acetate in pentane to give the title compound as a yellow oil (1.27 g, 86%).

Workup

additionThe reaction mix
temperaturewas cooled
custompartitioned between dichloromethane (30 ml) and brine (150 ml)
customThe organic layer was removed
filtrationfiltered
customthe solvent removed under reduced pressure
customThe resulting product was purified by flash column chromatography on a Biotage 40+M column
washeluting from 0-60% ethyl acetate in pentane

Sources & evidence

ORD record: ord-03c9d1df41fd407c8d42a2f72c61ffcc
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07642256B2

Reaction notes

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