Reaktion #352065

Reaktionsgleichung

citric acid

methacrylic acid butylamide

tetrahydrofuran

n-butyllithium

2(S)-tert-butoxy-carbonyl-amino-4(S)-isopropyl-5-(p-tert-butyl-phenyl)-pentanal

→

title compound

N-Tert-butoxycarbonyl-2-methylene-4(S)-hydroxy-5(S)-amino-7(S)-isopropyl-8-(p-tert-butyl-phenyl)-octanoic acid (N-butyl)amide

Lösungsmittel

hexane

diethyl ether

water

hexane

tetrahydrofuran furan

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe mixture is stirred for a further 15 minutes at -75° C.
2. 2
   workup.STIRRINGThe reaction mixture is then stirred further for 15 minutes at -75° C. and for 70 minutes at 0° C.
3. 3
   ExtraktionThe product is extracted repeatedly with diethyl ether
4. 4
   SonstigeThe diastereoisomeric mixture is separated by FC (700 g of silica gel, eluant: dichloromethane/diethyl ether=9:1)

Vorschrift

695 mg of methacrylic acid butylamide are dissolved in 30 ml of tetrahydrofuran and, at -75° C., 6.2 ml of 1.6M n-butyllithium in hexane are added thereto. The reaction mixture is stirred for 30 minutes at 0° C. and then, at -75° C., 9.8 ml of 1M chlorotitanium triisopropoxide in hexane are added thereto. The mixture is stirred for a further 15 minutes at -75° C. and then, at the same temperature, a solution of 924 mg of 2(S)-tert-butoxy-carbonyl-amino-4(S)-isopropyl-5-(p-tert-butyl-phenyl)-pentanal in 10 ml of tetrahydrofuran furan is added dropwise thereto. The reaction mixture is then stirred further for 15 minutes at -75° C. and for 70 minutes at 0° C. and then, in succession, 15 ml of 10% aqueous citric acid solution, water and diethyl ether are added thereto. The product is extracted repeatedly with diethyl ether. The diastereoisomeric mixture is separated by FC (700 g of silica gel, eluant: dichloromethane/diethyl ether=9:1). The title compound is obtained: diastereoisomer I: Rf (dichloromethane/diethyl ether=9:1)=0.21; diastereoisomer II: Rf (dichloromethane/diethyl ether=9:1)=0.14.

Quelle