Hydrochloric Acid → HCID 68490102, compound

Temperature

0 °C

Raney-Nickel (3.82 g, 50% in water, ˜32.5 mmol) and a large heavy oval stirring bar were placed in a 500 mL RBF. The water was removed via pipette and the Raney-Nickel was washed with methanol (2×10 mL). Then methanol (100 mL) and 258 (7.88 g, 25.0 mmol) were added and the mixture was cooled to 0° C. Hydrazine hydrate (6.30 g, 126 mmol) was added dropwise via syringe. The reaction mixture was stirred for 30 min at 0° C., then for 7 h at 50° C. The mixture was passed through a sinter funnel with celite to remove the Raney-Nickel. The sinter was washed with methanol (4×20 mL). The combined filtrates were concentrated in vacuo to receive the crude amine as brownish green oil (7.72 g) which was used without further purification. The crude amine (7.41 g, max. 24.0 mmol) was dissolved in dichloromethane (80 mL) and cooled to 0° C. Triethylamine (3.68 g, 36.4 mmol) was added, then acetic anhydride (2.96 g, 29.0 mmol) added dropwise via syringe. The reaction mixture was stirred for 4 h. Water (40 mL) and hydrochloric acid (5M, 10 mL) were added and the layers separated. The aqueous layer was extracted with dichloromethane (2×100 mL). The combined organic layers were washed with brine (80 mL), dried (MgSO4), filtered and concentrated in vacuo to give the title compound (8.73 g, >99%) as beige solid. 1H NMR (270 MHz, CDCl3) δ 0.83 (3H, t, J 7.4, CH2CH3), 1.09-1.27 (1H, m, one of CH2CH3), 1.32-1.50 (1H, m, one of CH2CH3), 1.87 (3H, s, NCOCH3), 2.64 (2H, d, J 6.3, ArCH2CH), 3.85 (3H, s, OCH3), 3.89-4.07 (1H, m, ArCH2CH), 5.08 (1H, d, br, J 8.8, NH), 5.13 (2H, s, OCH2Ph), 6.63-6.72 (2H, m, 2×CH), 6.77-6.82 (1H, m, CH), 7.24-7.44 (5H, m, OCH2C6H5).

1. customThe water was removed via pipette
2. washthe Raney-Nickel was washed with methanol (2×10 mL)
3. waitfor 7 h at 50° C
4. customThe mixture was passed through a sinter funnel with celite
5. customto remove the Raney-Nickel
6. washThe sinter was washed with methanol (4×20 mL)
7. concentrationThe combined filtrates were concentrated in vacuo
8. customwas used without further purification
9. temperaturecooled to 0° C
10. stirringThe reaction mixture was stirred for 4 h
11. customthe layers separated
12. extractionThe aqueous layer was extracted with dichloromethane (2×100 mL)
13. washThe combined organic layers were washed with brine (80 mL)
14. dry with materialdried (MgSO4)
15. filtrationfiltered
16. concentrationconcentrated in vacuo

ORD record

ord-cc551523723e4f85afc2dfe32c6be244

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08394825B2