Hydrochloric Acid → N-heptyl-2-(4-hydroxymethyl-phenyl)-acetamide

A stirred solution of (4-bromomethyl-phenyl)acetic acid (80.0 mmol, 12.0 g) and thionyl chloride (240 mmol, 17.5 mL) in chloroform (200 mL) under a nitrogen atmosphere was heated under reflux for 16 hours. The solution was cooled to room temperature and concentrated under reduced pressure to a white solid. The solid was dissolved in dichloromethane and added dropwise to a solution of 1-heptylamine (95.9 mmol, 14.2 mL) and N,N-diisopropylethylamine (95.9 mmol, 16.7 mL) in dichloromethane (100 mL) cooled to 0° C. The resulting solution was stirred at room temperature for 25 minutes. The mixture was poured over 1N HCl, and the aqueous layer was extracted with dichloromethane (2×). The organic layers were combined, washed with 2N HCl (2×), brine (1×), dried over anhydrous sodium sulfate and concentrated to give a white solid. A stirred solution of this solid (˜24.7 mmol, 7.5 g) and CaCO3(120 mmol, 12.0 g) in a 1:1 H2O/dioxane mixture (150 mL) was brought to reflux for 3 hours. The solution was cooled to room temperature and concentrated to a white residue. Water and dichloromethane were added and the remaining solid was dissolved by the addition of 6N HCl. The aqueous layer was isolated and extracted with dichloromethane (2×). The organic layers were combined, washed with brine (1×), dried over anhydrous sodium sulfate, and concentrated to give a yellow oil. The oil was purified by chromatography on silica gel (Merck silica gel 60, art#9385-3) eluting with 10% CH3OH in dichloromethane to give N-heptyl-2-(4-hydroxymethyl-phenyl)-acetamide as a white solid (1.5 g, 24%).

1. temperatureunder reflux for 16 hours
2. concentrationconcentrated under reduced pressure to a white solid
3. dissolutionThe solid was dissolved in dichloromethane
4. temperaturecooled to 0° C
5. extractionthe aqueous layer was extracted with dichloromethane (2×)
6. washwashed with 2N HCl (2×), brine (1×)
7. dry with materialdried over anhydrous sodium sulfate
8. concentrationconcentrated
9. customto give a white solid
10. temperatureto reflux for 3 hours
11. temperatureThe solution was cooled to room temperature
12. concentrationconcentrated to a white residue
13. additionWater and dichloromethane were added
14. dissolutionthe remaining solid was dissolved by the addition of 6N HCl
15. customThe aqueous layer was isolated
16. extractionextracted with dichloromethane (2×)
17. washwashed with brine (1×)
18. dry with materialdried over anhydrous sodium sulfate
19. concentrationconcentrated
20. customto give a yellow oil
21. customThe oil was purified by chromatography on silica gel (Merck silica gel 60, art#9385-3)
22. washeluting with 10% CH3OH in dichloromethane

ORD-Eintrag

ord-01890fa24cbb41b4a04be7d7bb12a81b

Quelldatensatz

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06699904B2