Diisopropylethylamine → N-(1-(Phenylmethyl)piperid-4-yl)-N-(3-phenyl-2-propen-1-yl)-4-methoxyphenylacetamide

To a solution of 4-amino-N-benzylpiperidine (200 mg, 1.05 mmol) in methanol (2 ml) was added trans-cinnamaldehyde (211 mg, 1.6 mmol), followed by Acetic acid in methanol (1 M, 1.4 ml) and sodiumcyanoborohydride in methanol (0.3 M, 4.4 ml). The reaction mixture was stirred at room temperature. After 48 h, water (2 ml) was added. The mixture was stirred for another 2 h before concentrated and redissolved in diethyl ether (20 ml). The organic layer was extracted with HCl (0.1 N, 2×10 ml). The combined aqueous layers were treated with NaOH (0.2 N) until basic (pH>8). The mixture was extracted with dichloromethane (2×10 ml). The combined organic layers were dried (Na2SO4) and concentrated. The crude product, which was used without any further purification, was dissolved in dichloromethane (5 ml). Diisopropylethylamine (284 mg, 2.1 eq.) was added, followed by 4-methoxyphenylacetyl chloride (387 mg, 2.0 eq). The reaction mixture was stirred at room temperature. After 18 h, water (2 ml) was added. After additional 2 h dichloromethane (10 ml) was added. The mixture was extracted with NaOH (0.2 N, 3×15 ml), and water (15 ml). The organic layer was dried (Na2SO4) and concentrated. The crude product was redissolved in methanol (2 ml) and added on to a column carrying strongly acidic cation exchange resin (0.3 mmol/g resin), which was washed with methanol (3×6 ml), and eluted with 10% NH3 in methanol, and concentrated to give the title compound. 13C-NMR (CDCl3): δ 28.5, 38.1, 46.6, 47.4, 50.9, 54.7, 62.9, 113.7, 125.5, 126.4, 126.6, 127.4, 127.9, 128.5, 128.6, 129.6, 130.0, 135.2, 135.3, 138.0, 158.2, 173.2.

1. stirringThe mixture was stirred for another 2 h
2. concentrationbefore concentrated
3. dissolutionredissolved in diethyl ether (20 ml)
4. extractionThe organic layer was extracted with HCl (0.1 N, 2×10 ml)
5. additionThe combined aqueous layers were treated with NaOH (0.2 N) until basic (pH>8)
6. extractionThe mixture was extracted with dichloromethane (2×10 ml)
7. dry with materialThe combined organic layers were dried (Na2SO4)
8. concentrationconcentrated
9. customThe crude product, which was used without any further purification
10. dissolutionwas dissolved in dichloromethane (5 ml)
11. stirringThe reaction mixture was stirred at room temperature
12. waitAfter 18 h
13. extractionThe mixture was extracted with NaOH (0.2 N, 3×15 ml), and water (15 ml)
14. dry with materialThe organic layer was dried (Na2SO4)
15. concentrationconcentrated
16. dissolutionThe crude product was redissolved in methanol (2 ml)
17. additionadded on to a column
18. washwas washed with methanol (3×6 ml)
19. washeluted with 10% NH3 in methanol
20. concentrationconcentrated

ORD record

ord-f8a01bcc4e7a44b8b5bd2ad5ac5e2adf

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296694B2