Water → 3-(3-Hexyl-6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenylamine

Temperature

50 °C

To a solution of 3-hexyl-6-methyl-6-(3-nitrophenyl)-3-azabicyclo[3.1.0]hexan-2-one (Preparation 11, 10.7 g, 33.86 mmol) in tetrahydrofuran (500 ml) under nitrogen, was added dropwise over 1 h at room temperature a 1.0 M solution of lithium aluminium hydride in tetrahydrofuran (100 ml, 100 mmol). The mixture was heated to 50° C. for 2 h, then cooled to room temperature. Water (50 ml) was carefully added, and the mixture was stirred for 1 h, before the tetrahydrofuran was removed in vacuo. The aqueous residue was acidified by the addition of 2N hydrochloric acid (20 ml) and then basified with the addition of 2N sodium hydroxide solution (25 ml). The mixture was extracted with ethyl acetate (3×250 ml). The combined extracts were dried (MgSO4), filtered and concentrated in vacuo. The residue was dissolved in ethanol (450 ml), Raney nickel (500 mg) was added, and the mixture was placed under an atmosphere of hydrogen (2 atm, 203 kPa) and stirred at 50° C. for 24 hours. The mixture was filtered through Celite™, and concentrated in vacuo. The residue was purified by silica column chromatography, eluting with 80:20:2 ethyl acetate/methanol/ammonia solution (0.880). Product-containing fractions were combined and concentrated in vacuo to give the title compound as a colourless oil (3.3 g, 36%).

1. temperaturecooled to room temperature
2. customwas removed in vacuo
3. additionThe aqueous residue was acidified by the addition of 2N hydrochloric acid (20 ml)
4. additionbasified with the addition of 2N sodium hydroxide solution (25 ml)
5. extractionThe mixture was extracted with ethyl acetate (3×250 ml)
6. dry with materialThe combined extracts were dried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. dissolutionThe residue was dissolved in ethanol (450 ml)
10. additionRaney nickel (500 mg) was added
11. filtrationThe mixture was filtered through Celite™
12. concentrationconcentrated in vacuo
13. customThe residue was purified by silica column chromatography
14. washeluting with 80:20:2 ethyl acetate/methanol/ammonia solution (0.880)
15. concentrationconcentrated in vacuo

ORD record

ord-30ff08a1c2e54995a723d02ef6ae55ef

Source dataset

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06313312B1