tert-butyl 2-oxopyrrolidine-1-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,1-dimethylethyl 2-oxo-1-pyrrolidinecarboxylate (7.5 g, 40.5 mmol) in dry tetrahydrofuran (150 ml) under a nitrogen atmosphere and at −78° C., was treated dropwise with a solution of isobutyl magnesium bromide in diethyl ether (2 molar, 22.5 ml, 45 mmol). The mixture was stirred at −78° C. for 2h then quenched into a saturated aqueous solution of ammonium chloride (100 ml). The products were extracted into ethyl acetate (2×250 ml) and the combined extracts dried over magnesium sulphate. Concentration of the extracts gave an oil which was purified on silica gel using isohexane/diethylether (1:1). The title compound was isolated as a colourless oil (2.3 g, 25%). then quenched into a saturated aqueous solution of ammonium chloride (100 ml) The products were extracted into ethyl acetate (2×250 ml) the combined extracts dried over magnesium sulphate Concentration of the extracts gave an oil which was purified on silica gel

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 250 mL round-bottom flask, tert-butyl 2-oxopyrrolidine-1-carboxylate (4.12 g, 22.2 mmol) was combined with 25 mL of THF and cooled to −78° C. Lithium diisopropylamide (1.5M in THF) (14.8 mL, 22.2 mmol) was added slowly and the mixture was agitated for 30 minutes. 2,3-Dibromopropene (2.72 mL, 22.2 mmol) was added and the mixture was agitated overnight and allowed to warm to ambient temperature. The reaction was then quenched with sodium bicarbonate solution and extracted twice with ether. The extracts were washed with brine and evaporated. The crude product was purified by column chromatography, eluting with 20% ethyl acetate/hexane, to provide the title compound (0.560 g, 8.3% yield). the mixture was agitated overnight to warm to ambient temperature The reaction was then quenched with sodium bicarbonate solution extracted twice with ether The extracts were washed with brine evaporated The crude product was purified by column chromatography eluting with 20% ethyl acetate/hexane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (7.03 g, 38 mmol) in THF (130 mL) was added phenylmagnesium bromide (1.0 M solution, 50 mL) at −78° C. After stirring for 2 hour at −78° C., HCl (2 M, 35 mL) was added to quench the reaction, which was then warmed to room temperature and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organics were washed with brine (50 mL) and dried over Na2SO4, filtered and concentrated under reduced pressure to afford 9.56 g (96% yield) of the desired product. to quench the reaction, which was then warmed to room temperature the aqueous layer was extracted with EtOAc (2×100 mL) The combined organics were washed with brine (50 mL) dried over Na2SO4 filtered concentrated under reduced pressure