Cyclohexylamine → 3-Bromo-1-cyclohexylpyrrolidin-2-one

Temperature

0 °C

Dissolve 2,4-dibromo-butyryl chloride (17.0 g, 64.3 mmol) in chloroform (3 ml) and add to a mixture of cyclohexylamine (7.65 g, 77.2 mmol) in chloroform (20 mL) and H2O (3 mL) at 0° C. Add sodium hydroxide (5.92 g, 147.9 mmol) slowly while keeping the reaction temperature below 10° C. Stir for 1 hour. Wash the organic layer with 0.5M hydrochloride and brine. Dry over sodium sulfate, filter, and concentrate. Place the residue in THF (200 mL) and cool to 0° C. Add sodium hydride (1.02 g, 42.6 mmol) and stir for two days. Add additional sodium hydride (1.02 g, 42.6 mmol) and stir for 3 days. Pour onto water and ice and extract with methylene chloride. Dry over sodium sulfate, filter, and concentrate to yield 6.36 g (34%) of the title compound: NMR (CDCl3) δ 4.41 (dd, 1H), 3.94 (m, 1H), 3.48 (m, 1H), 3.33 (m, 1H), 2.51 (m, 1H), 2.30 (m, 1H), 1.82 (m, 3H), 1.70 (m, 2H), 1.38 (m, 4H), 1.11 (m, 1H).

1. customthe reaction temperature below 10° C
2. washWash the organic layer with 0.5M hydrochloride and brine
3. dry with materialDry over sodium sulfate
4. filtrationfilter
5. concentrationconcentrate
6. stirringstir for 3 days
7. additionPour onto water and ice
8. extractionextract with methylene chloride
9. dry with materialDry over sodium sulfate
10. filtrationfilter
11. concentrationconcentrate

ORD record

ord-e4d526df5a914501b6ad83880175e44f

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07713979B2