Bromide ion → HCID 59632303, compound

Participants

Reaction Conditions

Reaction Steps

To a cold (−78° C.) solution of 2-(5-(4-bromo-2-methylphenyl)-1-(2,6-dichlorophenyl)-1H-pyrazol-3-yl)propan-2-ol (215 mg, 0.49 mmol) in a mixture of THF (4 mL) and Et2O (4 mL) was added lithium bis(trimethylsilyl)amide (0.5 mL of a 1.0M solution in THF, 0.5 mmol). After several minutes stirring at −78° C. the resulting alkoxide solution was treated with n-butyllithium (1.0 mL of a 1.6M solution in hexane, 1.6 mmol). After 10 minutes stirring at −78° C., LC/MS showed some starting bromide present in a quenched aliquot of the reaction. After 30 minutes additional n-butyllithium was added (0.5 mL of a 1.6M solution in hexane, 0.8 mmol). After an additional 15 minutes stirring at −78° C. the reaction mixture was treated with dry N,N-dimethylformamide (0.4 mL, 5.2 mmol). Several minutes after the addition of the DMF, the −78° C. bath was replaced with an ice bath and the reaction mixture was allowed to come to ambient temperature overnight. The reaction was quenched by the addition of saturated NH4Cl and diluted with EtOAc. The layers were separated and the aqueous was extracted with EtOAc (3×). Combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure to afford a yellow syrup. The crude product was purified by flash column chromatography eluting with 0% to 100% EtOAc/hexane to afford 4-(1-(2,6-dichlorophenyl)-3-(2-hydroxypropan-2-yl)-1H-pyrazol-5-yl)-3-methylbenzaldehyde which was carried on to the next step without further purification. MS(ES): 389 [M+H]+.

Provenance & Evidence