Sodium hydride → HCID 59632551, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of NaH (52 mg of a 60% dispersion in mineral oil) in THF (7.5 mL) cooled to 0° C. in an ice bath was added methyl 3-((dimethoxyphosphoryl)methyl)benzoate as a solution in THF (1 mL) followed by a THF (1 mL) rinse of the phosphonate vial and syringe to insure complete transfer. The ice bath was removed and the reaction was allowed to warm to ambient temperature. After 90 minutes at ambient temperature, 4-(1-(2,6-dichlorophenyl)-3-(2-hydroxypropan-2-yl)-1H-pyrazol-5-yl)-3-methylbenzaldehyde (0.49 mmol impure from previous step) was added via cannula to the reaction mixture followed by a THF (1 mL) rinse of the flask and cannula after 1 hour-45 minutes at ambient temperature the reaction was quenched by addition of saturated aqueous NH4Cl and 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 a gradient from 0% to 40% MeCN/CH2Cl2 to afford (E)-methyl 3-(4-(1-(2,6-dichlorophenyl)-3-(2-hydroxypropan-2-yl)-1H-pyrazol-5-yl)-3-methylstyryl)benzoate (180 mg, 70% yield) of slightly impure product. This material was carried on to the ester hydrolysis without further purification. MS(ES): 521 [M+H]+.

Provenance & Evidence