Reaktion #76066

Reaktionsgleichung

1-heptylamine

N,N-diisopropylethylamine

CaCO3

HCl

(4-bromomethyl-phenyl)acetic acid

thionyl chloride

→

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

Ausbeute 24.0%

Lösungsmittel

dichloromethane

H2O dioxane

chloroform

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturunder reflux for 16 hours
2. 2
   Einengenconcentrated under reduced pressure to a white solid
3. 3
   workup.DISSOLUTIONThe solid was dissolved in dichloromethane
4. 4
   Temperaturcooled to 0° C
5. 5
   Extraktionthe aqueous layer was extracted with dichloromethane (2×)
6. 6
   Waschenwashed with 2N HCl (2×), brine (1×)
7. 7
   Trocknendried over anhydrous sodium sulfate
8. 8
   Einengenconcentrated
9. 9
   Sonstigeto give a white solid
10. 10
    Temperaturto reflux for 3 hours
11. 11
    TemperaturThe solution was cooled to room temperature
12. 12
    Einengenconcentrated 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
    SonstigeThe aqueous layer was isolated
16. 16
    Extraktionextracted with dichloromethane (2×)
17. 17
    Waschenwashed with brine (1×)
18. 18
    Trocknendried over anhydrous sodium sulfate
19. 19
    Einengenconcentrated
20. 20
    Sonstigeto give a yellow oil
21. 21
    SonstigeThe oil was purified by chromatography on silica gel (Merck silica gel 60, art#9385-3)
22. 22
    Wascheneluting with 10% CH3OH in dichloromethane

Vorschrift

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%).

Quelle