Acetic Anhydride → (R)(+)-N-(1,2,3,4-Tetrahydro-1-naphthyl)-N-methylformamide

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Reaction Conditions

Reaction Steps

Acetic anhydride (54.1 g) was chilled to 0° C. and stirred as 98% formic acid (33.1 g) was added over 30 minutes, keeping the temperature below 5° C. The solution was warmed to 50° C., held at this temperature for 15 minutes, and chilled to 5° C. The resulting solution of acetic-formic anhydride was added over 5 minutes to a stirred, chilled solution of (R)(-)-N-methyl-1,2,3,4-tetrahydro-1-naphthylamine (19.08 g) in 98% formic acid (19.08 ml), keeping the temperature below 10° C. The reaction solution was warmed to room temperature, stirred for 1 hour, poured into an ice-water mixture (200 g) and stirred for 30 minutes. The mixture was basified to pH 9 with 10N aqueous sodium hydroxide solution (about 230 ml) and extracted with dichloromethane (3×200 ml). The combined extracts were back-washed with 1N aqueous hydrochloric acid (100 ml), then water (100 ml), and evaporated under vacuum to give the title compound (21.63 g, 96.6%) as a solid, m.p. 53°-55° C.; Rf 0.80 (silica; chloroform, methanol; 95:5).

Provenance & Evidence