Hydrochloric Acid → HCID 54099212, compound

Participants

Reaction Conditions

Reaction Steps

BOC-L-Valine (31.4 g) and N-methylmorpholine (15.9 ml) are dissolved in tetrahydrofuran (250 ml) and cooled to −20° C. Isobutyl chloroformate (18.9 ml) is added dropwise during 20 minutes. The resulting mixture is stirred for 15 min and allowed to warm to −7° C. It is then cooled again to −20° C. and a solution of 2-{4-[3-(4-chloro-phenyl)-allyloxy]-3-methoxy-phenyl}-ethylamine (41.7 g) in tetrahydrofuran (150 ml) is added dropwise during 40 min. The reaction mixture is stirred at room temperature during 4 hours. 1M Hydrochloric acid (500 ml) is added carefully. It is extracted with ethyl acetate (2×500 ml). The organic layers are washed with 1M hydrochloric acid (500 ml) and brine (500 ml), dried (MgSO4) and evaporated. The residue is dissolved in tetrahydrofuran (500 ml) and hydrogenated over palladium (5% on charcoal, 0.14 g) at room temperature and normal pressure. The reaction mixture is filtered and evaporated. The residue is dissolved in dioxane (130 ml) and added dropwise to 4M sulfuric acid (650 ml). The resulting mixture is stirred for 8 hours at +50° C. After cooling it is extracted with diethyl ether (2×1000 ml). The aqueous phase is saturated with potassium carbonate and then extracted with diethyl ether (2×1500 ml). The organic layers are dried (K2CO3) and evaporated. (S)-2-Amino-N-(2-{4-[3-(4-chloro-phenyl)-propoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide is obtained.

Provenance & Evidence