Hydrochloric Acid → 6-Bromo-3-(5-fluoropyrimidin-4-yl)-2-[(1R)-1-(4-methoxyphenyl)ethyl]-3-methyl-isoindolin-1-one

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Reaction Steps

Dissolve 6-bromo-2-[(1R)-1-(4-methoxyphenyl)ethyl]-3-methyl-isoindolin-1-one (2.814 mmol, 1.014 g) in tetrahydrofuran (28 mL). Add 4-chloro-5-fluoro-pyrimidine (5.628 mmol, 518 μL) and cool to 0° C. Add potassium hexamethyldisilazide (4.502 mmol, 9 mL, 0.5 M in toluene) over 7 minutes and stir for 1 hour, then warm to ambient temperature and stir for 90 minutes. Pour into methyl-tert-butyl ether and aqueous 1 M HCl, add water and separate the layers. Wash with aqueous 1 N HCl, filter, wash with saturated aqueous sodium chloride, dry over magnesium sulfate, filter through a 2 cm pad of silica gel, and evaporate under reduced pressure to provide an oil. Purify on silica gel with 20-40% ethyl acetate/hexane to give the title compound as a foam (547 mg, 43%). ES/MS m/z: 456 (M+H).

Provenance & Evidence