Sodium bis(trimethylsilyl)amide → (3R,5R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3-hydroxypyrrolidin-2-one

Temperature

-78 °C

(S)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)pyrrolidin-2-one (40 g, 120 mmol) was dissolved in anhydrous THF (400 mL) and stirred at −78° C. under nitrogen To this was added 1.5 eq of a 2.0M THF solution of sodium bis(trimethylsilyl)amide dropwise over 5 minutes. The light yellow mixture was stirred for 20 minutes under nitrogen at −78° C., followed by the slow dropwise addition of oxaziridine (53 g, 180 mmol) as a 200 mL solution in THF. The mixture was stirred for 0.5 hour. The reaction was quenched with saturated aqueous NH4Cl, and the mixture was extracted with EtOAc (1 L). The extract was washed with 1N HCl (1 L), dried over MgSO4, and concentrated to a 500 mL volume. The precipitated white solid was filtered, the filtrate was concentrated to remove solvent after the addition of silica gel (200 g). The residue was put on a column (8×80 cm) of silica gel (900 g), which was previously packed in hexanes. Elution was carried out initially with DCM:hexanes (1:1). Once the oxaziridine and imine were completely collected, the column was eluted with DCM to obtain (3R,5R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3-hydroxypyrrolidin-2-one (21 g, 98% purity) as yellow oil.

1. stirringThe light yellow mixture was stirred for 20 minutes under nitrogen at −78° C.
2. stirringThe mixture was stirred for 0.5 hour
3. customThe reaction was quenched with saturated aqueous NH4Cl
4. extractionthe mixture was extracted with EtOAc (1 L)
5. washThe extract was washed with 1N HCl (1 L)
6. dry with materialdried over MgSO4
7. concentrationconcentrated to a 500 mL volume
8. filtrationThe precipitated white solid was filtered
9. concentrationthe filtrate was concentrated
10. customto remove solvent
11. additionafter the addition of silica gel (200 g)
12. washElution
13. customOnce the oxaziridine and imine were completely collected
14. washthe column was eluted with DCM

ORD record

ord-b0c1b67f6e224a768edc31e1225550ef

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09388145B2