Methyl iodide → Methyl (2S,3S)-3-[(tert-Butoxycarbonyl)amino]-2-methyl-4-oxo-4-pyrrolidin-1-ylbutanoate

Temperature

-78 °C

To a stirred solution of the product from Example 1, Step A (2.2 g, 7.33 mmol) in THF (30 mL) was added lithium hexamethyldisilazide (16.0 mL, 1M in THF, 16.0 mmol) at −78° C. The resulting mixture was stirred at −78° C. for 30 min. Iodomethane (2.8 mL, 45.0 mmol) was then added. After stirring at −78° C. for 2 h, the reaction was quenched with saturated aqueous ammonium chloride solution. The organic phase was separated and the aqueous phase was extracted with two portions of ethyl acetate. The combined organic layers were washed with brine and concentrated in vacuo. Purification by flash chromatography (30:70 hexanes/ethyl acetate) afforded the desired product (major diastereoisomer from the reaction).

1. stirringAfter stirring at −78° C. for 2 h
2. customthe reaction was quenched with saturated aqueous ammonium chloride solution
3. customThe organic phase was separated
4. extractionthe aqueous phase was extracted with two portions of ethyl acetate
5. washThe combined organic layers were washed with brine
6. concentrationconcentrated in vacuo
7. customPurification by flash chromatography (30:70 hexanes/ethyl acetate)

ORD record

ord-34a4024ed9164870b34378832f1471d7

Source dataset

uspto-grants-2010_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07687492B2