Hydrochloric Acid → HCID 59432806, compound

A mixture of (benzhydrylidene-amino)acetic acid ethyl ester (20 g, 74.8 mmol), 4-bromo-1-butene (10.1 g, 74.8 mmol), K2CO3 (31.0 g, 224 mmol), tetrabutylammonium bromide (2.41 g, 7.48 mmol), and acetonitrile (150 mL) was heated at reflux for 6 h. The reaction was cooled to rt and filtered through a sintered glass funnel. The filtrate was concentrated in vacuo. The residue was dissolved in diethyl ether (250 mL) and a white solid precipitated. The solid was removed by vacuum filtration. A solution of 1 N HCl (150 mL) was added to the filtrate, which contained the crude product (2-(benzhydrylidene-amino)-hex-5-enoic acid ethyl ester). The resulting biphasic mixture was stirred vigorously for 18 h. The mixture was transferred to a separatory funnel The aqueous layer was collected and concentrated in vacuo. The residue was dissolved in toluene (2×200 mL) and reconcentrated. The crude amino ester was dissolved in CH2Cl2 and reacted with 4-chlorobenzenesulfonyl chloride (15.8 g, 74.8 mmol) and Et3N (31.2 mL, 224 mmol). After 18 h, the resulting mixture was poured into 1 N HCl (500 mL). The organic layer was collected and washed sequentially with 1 N HCl (500 mL) and brine (50 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude concentrate was purified using silica gel column chromatography (5:1, hexanes/EtOAc) to afford 5.57 g (23% yield over 3 steps) of the title compound: LCMS (M+Na)+354.0; 1H NMR (400 MHz, DMSO-d6) δ 8.47 (d, 1H, J=8.8), 7.76 (d, 2H, J=8.8), 7.66 (d, 2H, J=8.8), 5.69 (m, 1H), 4.95-4.88 (m, 2H). 3.86 (q, 2H, J=7.1), 3.76 (m, 1H), 1.98 (m, 2H), 1.71-1.54 (m, 2H), 1.03 (t, 3H, J=7.1).

1. temperaturewas heated
2. temperatureat reflux for 6 h
3. filtrationfiltered through a sintered glass funnel
4. concentrationThe filtrate was concentrated in vacuo
5. dissolutionThe residue was dissolved in diethyl ether (250 mL)
6. customa white solid precipitated
7. customThe solid was removed by vacuum filtration
8. additionA solution of 1 N HCl (150 mL) was added to the filtrate, which
9. customThe mixture was transferred to a separatory funnel
10. customThe aqueous layer was collected
11. concentrationconcentrated in vacuo
12. dissolutionThe residue was dissolved in toluene (2×200 mL)
13. dissolutionThe crude amino ester was dissolved in CH2Cl2
14. waitAfter 18 h
15. customThe organic layer was collected
16. washwashed sequentially with 1 N HCl (500 mL) and brine (50 mL)
17. dry with materialThe organic layer was dried over MgSO4
18. filtrationfiltered
19. concentrationconcentrated in vacuo
20. concentrationThe crude concentrate
21. customwas purified

ORD record

ord-4d86a94f3c2249169a4f462d89d3bb57

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08513253B2