Lithium Hexamethyldisilazide → (2S,4R)-di-tert-butyl 4-(4-fluoro-2-methylbenzyl)-5-oxopyrrolidine-1,2-dicarboxylate

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Reaction Conditions

Reaction Steps

Step (c) (S)-Di-tert-butyl 5-oxopyrrolidine-1,2-dicarboxylate (1.15 g, 4.0 mmol) was dissolved in dry THF (20 mL) and the solution was cooled to −78° C. A solution of LiHMDS (1M in hexanes, 4.4 mL, 4.4 mmol) then was added dropwise under nitrogen. The mixture was cooled at −78° C. for 40 minutes and then a solution of 2-methyl-4-fluorobenzyl bromide (975 mg, 4.8 mmol) in THF (5 mL) was added slowly. The mixture was stirred at −78° C. for 2 hours and then quenched with saturated ammonium chloride (20 mL). The mixture was extracted with diethyl ether (3×70 mL) and the combined extract was washed with brine (30 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. Product was purified from the residue by flash column (eluted with a 4:1 hexanes/diethyl ether mixture) to give (2S,4R)-di-tert-butyl 4-(4-fluoro-2-methylbenzyl)-5-oxopyrrolidine-1,2-dicarboxylate (810 mg, 2.0 nmol, 49.7%), clean as a white solid.

Provenance & Evidence