Reacción #76066

Ecuación de reacción

1-heptylamine

N,N-diisopropylethylamine

CaCO3

HCl

(4-bromomethyl-phenyl)acetic acid

thionyl chloride

→

N-heptyl-2-(4-hydroxymethyl-phenyl)-acetamide

Rendimiento 24.0%

Disolventes

dichloromethane

H2O dioxane

chloroform

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturaunder reflux for 16 hours
2. 2
   Concentraciónconcentrated under reduced pressure to a white solid
3. 3
   workup.DISSOLUTIONThe solid was dissolved in dichloromethane
4. 4
   Temperaturacooled to 0° C
5. 5
   Extracciónthe aqueous layer was extracted with dichloromethane (2×)
6. 6
   Lavadowashed with 2N HCl (2×), brine (1×)
7. 7
   Secadodried over anhydrous sodium sulfate
8. 8
   Concentraciónconcentrated
9. 9
   Otroto give a white solid
10. 10
    Temperaturato reflux for 3 hours
11. 11
    TemperaturaThe solution was cooled to room temperature
12. 12
    Concentraciónconcentrated to a white residue
13. 13
    workup.ADDITIONWater and dichloromethane were added
14. 14
    workup.DISSOLUTIONthe remaining solid was dissolved by the addition of 6N HCl
15. 15
    OtroThe aqueous layer was isolated
16. 16
    Extracciónextracted with dichloromethane (2×)
17. 17
    Lavadowashed with brine (1×)
18. 18
    Secadodried over anhydrous sodium sulfate
19. 19
    Concentraciónconcentrated
20. 20
    Otroto give a yellow oil
21. 21
    OtroThe oil was purified by chromatography on silica gel (Merck silica gel 60, art#9385-3)
22. 22
    Lavadoeluting with 10% CH3OH in dichloromethane

Procedimiento

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%).

Fuente