Reaktion #58653

Reaktionsgleichung

CH2Cl2

Benzyl 2-(4-chlorobenzyl)-3-ketobutyrate

ammonia

sodium cyanoborohydride

→

Benzyl 3-amino-2-(4-chlorobenzyl)butyrate

Lösungsmittel

MeOH

MeOH

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe excess sodium cyanoborohydride was destroyed by the addition of 6M HCl (to pH 1)
2. 2
   SonstigeThe residue obtained
3. 3
   Sonstigeafter removal of volatiles
4. 4
   Extraktionextracted with ether
5. 5
   Extraktionsaturated with sodium chloride and then extracted with EtOAc
6. 6
   SonstigeThis material was used in the ensuing coupling reaction without further purification

Vorschrift

Benzyl 2-(4-chlorobenzyl)-3-ketobutyrate (317 mg, 1 mmole, obtained from Step A) was added to a cooled mixture of 7M ammonia in MeOH (2.42 mL) and glacial acetic acid (1.6 mL). To this solution, at ˜10° C., was added sodium cyanoborohydride (101 mg, 1.75 mmol) in small portions. This mixture was stirred at room temperature for 40 h. The excess sodium cyanoborohydride was destroyed by the addition of 6M HCl (to pH 1). The residue obtained after removal of volatiles was taken up in a minimal amount of water and extracted with ether. The aqueous layer was basified to pH 10 using solid KOH. This layer was then saturated with sodium chloride and then extracted with EtOAc. Further analyses of the ether and the EtOAc layers suggest that the desired product resides the EtOAc layer. This material was used in the ensuing coupling reaction without further purification. Proton NMR spectrum show that the two pairs of diastereomers are obtained in ˜1:1 ratio, homogeneous by TLC, Rf=0.4 in 95:5 CH2Cl2:MeOH. LC/MS m/e=318 (M+1). 400 MHz 1H NMR (CDCl3) δ 1.27, 1.29 (2 d, J=7Hz, 3H), 2.85 (m, 1H), 3.03 (m, 1H), 3.15 (m, 1H), 3.55 (m, 1H), 4.85 (br, 2H), 5.00-5.18 (m, 2H), 7.0-7.2 (m, 9H).

Quelle