Benzyl chloroformate → Benzyl 3,3-dimethyl-2-oxopyrrolidine-1-carboxylate

Temperature

-78 °C

In an oven-dried 1000 ml flask under argon was dissolved 3,3-dimethyl-2-pyrrolidinone (0.0718 mol, 8.13 g) in 200 ml THF. The resulting solution was cooled to −78° C., and lithium hexamethyldisilazide (0.0790 mol, 79 ml of a 1M solution in THF) was added over 15 min. Stirring was continued for 30 minutes, at which time benzyl chloroformate (0.0790 mol, 13.5 g) was added and the reaction was allowed to warm to room temperature and stir for 16 hr. The mixture was concentrated to ⅓ total volume and diluted with 500 ml ethyl acetate and washed with 1M HCl (2×200 ml), water (1×200 ml), and brine (1×100 ml). The organic phase was dried over MgSO4, filtered and concentrated. Purification of the crude residue on 120 g silica (ethyl acetate/hexanes) yielded 12.3 g (69%) of phenylmethyl 3,3-dimethyl-2-oxo-1-pyrrolidinecarboxylate as a light yellow oil. LCMS (ESI+)=248 m/z (M+), 270 m/z (MNa+). 1H NMR (400 MHz, CDCl3) δ 7.48-7.46 (m, 2H), 7.39-7.36 (m, 3H), 5.31 (s, 2H), 3.77-3.73 (t, 2H, J=6.96 Hz), 1.91-1.88 (t, 2H, J=7.08 Hz), 1.23 (s, 6H). 13C NMR (CDCl3) δ 178.83, 151.86, 135.35, 128.60, 128.34, 128.10, 68.00, 42.79, 42.16, 32.95, 24.28.

1. additionwas added
2. temperatureto warm to room temperature
3. stirringstir for 16 hr
4. concentrationThe mixture was concentrated
5. additiondiluted with 500 ml ethyl acetate
6. washwashed with 1M HCl (2×200 ml), water (1×200 ml), and brine (1×100 ml)
7. dry with materialThe organic phase was dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification of the crude residue on 120 g silica (ethyl acetate/hexanes)

ORD record

ord-87aebbd1cdde4f6992c2d5e56bc9cde5

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07982053B2