2-Chloro-5-trifluoroacetylthiophene → 1-(5-Chlorothiophen-2-yl)-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanol

HRID 244425Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[N:6]=[CH:5]2.C([Li])CCC.[Cl:23][C:24]1[S:25][C:26]([C:29](=[O:34])[C:30]([F:33])([F:32])[F:31])=[CH:27][CH:28]=1>C1COCC1.O>[Cl:23][C:24]1[S:25][C:26]([C:29]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[N:7]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[N:6]=[CH:5]3)([OH:34])[C:30]([F:31])([F:32])[F:33])=[CH:27][CH:28]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a chilled (−78° C.) stirred solution of 1.5 g (5.0 mmol) of 5-bromo-1-(4-fluorophenyl)-1H-indazole in THF was added 2.0 mL (5.0 mmol) of n-butyllithium dropwise followed by 1.0 g (4.6 mmol) of 2-chloro-5-trifluoroacetylthiophene in one portion. After 30 minutes, the mixture was diluted with 10 mL of water, warmed to room temperature and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography using ethyl acetate-hexanes (gradient 10-30%) to afford 300 mg (15.5%) of the title compound. MS m/z 427.82 (MH+).

Workup

temperaturewarmed to room temperature
extractionextracted with ethyl acetate
washThe combined organic layers were washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by flash chromatography

Sources & evidence

ORD record: ord-9004be7ed1c449df989909ccd852b7a8
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658637B2

Reaction notes

Loading…