1-Pyrrolidinecarboxylic acid, 2-oxo-, 1,1-dimethylethyl ester → Tert-butyl 2-(2,5-difluorophenyl)-2-hydroxypyrrolidine-1-carboxylate

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Reaction Conditions

Reaction Steps

In step 6A-1, (2,5-difluorophenyl)magnesium chloride (6-1) was added drop-wise to a solution of tert-butyl 2-oxopyrrolidine-1-carboxylate (6-2) (9.6 g, 52 mmol) in THF under argon at −78° C. A maximum of 5 mL aliquots was used to minimize the temperature increase of the magnesium chloride reagent. The resulting solution was then stirred at −78° C. for one hour. The solution was then warmed to room temperature and quenched with concentrated HCl (4 mL). The solvent was then removed using a rotary evaporator resulting in a light yellow residue. The residue was then reconstituted in ethyl acetate and extracted with brine (3×150 mL). The organic layer was then dried using sodium sulfate. The ethyl acetate was removed yielding tert-butyl 2-(2,5-difluorophenyl)-2-hydroxypyrrolidine-1-carboxylate (6-3) as a light yellow oil. m/z=300 [M+1] The product was used without further purification.

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