Reaktion #1332300

Reaktionsgleichung

5-chloro-2-(3,5-dimethyl-piperidin-1-yl)-benzoic acid

(2S)-amino-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid methyl ester hydrochloride

HBTU

DIEA

→

2-[5-Chloro-2-(3,5-dimethyl-piperidin-1-yl)-benzoylamino]-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid methyl ester

Ausbeute 78.1%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe crude product was purified by flash column chromatography on silica gel

Vorschrift

A solution of 5-chloro-2-(3,5-dimethyl-piperidin-1-yl)-benzoic acid (0.250 g, 0.933 mmol) in DMF (4.0 mL) was reacted with (2S)-amino-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid methyl ester hydrochloride (0.360 g, 0.933 mmol), HBTU (0.355 g, 0.933 mmol), and DIEA (0.500 mL, 2.800 mmol) by the general procedure A. The crude product was purified by flash column chromatography on silica gel using DCM (+20% hexane) to give 0.435 g (62%) of 2-[5-Chloro-2-(3,5-dimethyl-piperidin-1-yl)-benzoylamino]-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid methyl ester. A solution of this ester (0.200 g, 0.334 mmol) in THF (4.0 mL) was reacted with LiOH (0.050 g, 1.172 mmol) by the general procedure I to give 0.182 g (93%) of 2-[5-Chloro-2-(3,5-dimethyl-piperidin-1-yl)-benzoylamino]-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid as a white solid. LCMS: 584 (M+1)+. 1H NMR (CDCl3) 11.20 [d, 1H], 8.21 [d, 1H], 7.45 [m, 2H], 7.39 [m, 2H], 7.23 [m, 8H], 7.02 [m, 2H], 6.86 [m, 2H], 4.90 [m, 1H], 3.38 [dd, 5.60 Hz, 1H], 3.26 [dd, 1H], 2.80 [m, 2H], 2.16 [t, 1H], 2.04 [t, 1H], 1.70 [m, 2H], 1.43 [m, 1H], 0.76 [m, 6H], 0.58 [m, 1H].

Quelle