BENZOCAINE METHANETHIOSULFONATE synthesis

Yield:212207-24-4 38%

Reaction Conditions:

with dmap;dicyclohexyl-carbodiimide in N,N-dimethyl-formamide at 20; for 5 h;

Steps:

1

A solution of p-aminobenzoic acid (1.32 g; 9.6 mmol), 2-hydroxyethyl methanethiosulfonate (1 g; 6.4 mmol, prepared according to Boldyrev, et al., Zh. Organic. Khim.3:37 (1967)), DCC (1.98 g; 9.6 mmol) and DMAP (61 mg; 0.5 mmol) in DMF (15 mL) was stirred at room temperature for 5 hours. It was then filtered, evaporated, and allowed to stand at room temperature for 2 days. Silica gel (8 g) was added and the mixture was evaporated to dryness. The residual powder was applied to a column of silica gel and then eluted with CH2Cl2/methanol (97:3). The fractions containing 4-(4-aminophenyl)-4-oxo-3-oxabutyl methanethiosulfonate were combined, and evaporated to dryness. Crystallization from ethyl acetate afforded a white crystalline solid (670 mg; 2.44 mmol; 38% yield) with m.p. of 112-113° C. 1H NMR (500 MHz (CD3)2SO) δ7.63 (d, J=8.7 Hz, 2H), 6.56 (d, J=8.7 Hz, 2H), 6.00 (s, 2H), 4.44 (t, J=6.1 Hz, 2H); 3.56 (t, J=6.1 Hz, 2H), 3.56 (s, 3H). MS (NH3 DCI): m/z 293 [(M+NH4)O+, 84%], 276 [(M+H)+, 10%], 120 [100%].

References:

EP966304,2005,B1 Location in patent:Page/Page column 15-16