Ammonia → (R)-4-butylpyrrolidin-2-one

Temperature

-78 °C

To a solution of (R)-4-butyl-1-[(S)-1-phenylethyl]pyrrolidin-2-one (1.4 g, 5.7 mmol) in dry tetrahydrofuran (10 mL) at −78° C. was added condensed liquid ammonia (100 mL). Freshly cut sodium (0.66 g, 28.5 mmol) was added and the resulting mixture was stirred at −78° C. for 2 h. The reaction was quenched with solid ammonium chloride. Ammonia was evaporated by warming up the reaction mixture slowly to room temperature. Water (50 mL) was added and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The residue was purified by flash column chromatography (silica gel, 4:1 EtOAc/acetone) to afford 0.7 g (87%) of (R)-4-butylpyrrolidin-2-one as a colorless oil: [α]D=+0.95° (c=0.60, CH2Cl2) {lit. [α]D=−0.67° (c=0.60, CH2Cl2) for (S)-enantiomer, Meyers, A. I. and Snyder, L. 1993, J. Org. Chem. 58, 36-42}; 1H NMR (CDCl3) δ 6.07 (bs, 1 H), 3.48 (t, 1 H), 3.02 (t, 1 H), 2.45 (m, 2 H), 1.99 (m, 1 H), 1.22-1.50 (m, 6 H), 0.90 (t, 3 H). MS(ES) m/e 142 [M+H]+.

1. customThe reaction was quenched with solid ammonium chloride
2. customAmmonia was evaporated
3. temperatureby warming up the reaction mixture slowly to room temperature
4. additionWater (50 mL) was added
5. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
6. dry with materialThe combined organic extracts were dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by flash column chromatography (silica gel, 4:1 EtOAc/acetone)

ORD record

ord-c99be775d20c465397d1e069ad89ccd4

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07456211B2