Reaktion #364143

Reaktionsgleichung

3-hydroxy-2-phenyl-4-quinoline carboxylic acid

(S)-(−)-1-phenylpropylamine

dicyclohexylcarbodiimide

1-hydroxybenzotriazole

→

title compound

Ausbeute 48.7%

(S)-(−)-N-(α-ethylbenzyl)-3-hydroxy-2-phenyl-4-quinoline carboxamide

Ausbeute 48.7%

Lösungsmittel

methylene chloride

—

mixture

H2O

methylene chloride

THF MeCN

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwere added dropwise over 10 minutes period
2. 2
   workup.ADDITIONwere added dropwise
3. 3
   workup.STIRRINGthe reaction stirred overnight
4. 4
   workup.STIRRINGthe reaction stirred 30 minutes
5. 5
   Sonstigethe solvent was evaporated in vacuo to dryness
6. 6
   Filtrationthe precipitated dicyclohexylurea (DCU) was filtered off
7. 7
   Waschenthe filtrate washed with water, 20% citric acid, 5% NaHCO3, brine
8. 8
   Trocknenthe organic layer dried over Na2SO4
9. 9
   Sonstigethe solvent evaporated in vacuo
10. 10
    SonstigeThe residue was purified by silica-gel (60-240 mesh) flash column chromatography
11. 11
    Wascheneluting with a mixture of hexane/EtOAc 9:1
12. 12
    workup.ADDITIONcontaining
13. 13
    Temperaturincreasing amounts of EtOAc
14. 14
    SonstigeThe purified product was crystallized from i-PrOH

Vorschrift

2.49 g (9.4 mmols) of 3-hydroxy-2-phenyl-4-quinoline carboxylic acid (CAS [485-89-2]) were suspended in 150 ml of a mixture of THF/MeCN 7:3, respectively; 1.40 g (10.3 mmols) of 1-hydroxybenzotriazole (HOBT) were added to the suspension and then 1.27 g (9.4 mmols) of (S)-(−)-1-phenylpropylamine, dissolved in 20 ml of methylene chloride were added dropwise over 10 minutes period. The reaction mixture was stirred at room temperature for 30 minutes and then 2.13 g (10.3 mmols) of dicyclohexylcarbodiimide (DCC), dissolved in 20 ml of methylene chloride, were added dropwise and the reaction stirred overnight. 20 ml of H2O were added and the reaction stirred 30 minutes, then the solvent was evaporated in vacuo to dryness. The residue was taken up in EtOAc, the precipitated dicyclohexylurea (DCU) was filtered off and the filtrate washed with water, 20% citric acid, 5% NaHCO3, brine and the organic layer dried over Na2SO4 and the solvent evaporated in vacuo. The residue was purified by silica-gel (60-240 mesh) flash column chromatography, eluting with a mixture of hexane/EtOAc 9:1, containing increasing amounts of EtOAc, until the ratio 7:3. The purified product was crystallized from i-PrOH to yield 1.75 g of the title compound as a white solid.

Quelle