1194550-59-8

1289646-78-1

1194550-59-8

The general procedure for the synthesis of benzyl (S)-2-((tert-butoxycarbonyl)amino)-3-(3-(methylsulfonyl)phenyl)propanoate hydrochloride from benzyl (S)-2-amino-3-(3-(methylsulfonyl)phenyl)propanoate is as follows: firstly, using sodium bicarbonate (3 eq.) and tert-butyl dicarbonate (Boc2O, 1.1 eq.) in a solvent mixture of dioxane and water. tert-butoxycarbonyl (Boc) protection of the amino group of bromophenylalanine, and the reaction afforded compound 7 in 98% yield.Subsequently, the reaction was carried out by cuprous iodide (0.4 eq.), cesium carbonate (0.5 eq.), L-proline (0.8 eq.), and the sodium salt of methanesulfinic acid (3.9 eq.) in dimethylsulfoxide (DMSO) for 9 hr. at 95-100 °C, during which two Additional addition of cuprous iodide (0.2 eq.) and L-proline (0.4 eq.) introduced the methanesulfonyl functional group, which was isolated in 96% yield to give compound 8. Next, using benzyl alcohol (1.1 eq.), 4-dimethylaminopyridine (DMAP, 0.1 eq.) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC, 1.0 eq. ), the carboxylic acid group of compound 8 was converted to a benzyl ester to give compound 9 in 99% yield. Finally, the deprotection reaction of the amino group was carried out by adding a dioxane solution of 4N HCl to a dichloromethane solution of compound 9 at 0 °C to isolate the hydrochloride salt of the free amino group, compound 10, in 94% yield.