Methanol → p-Toluenesulfonic acid

Participants

Reaction Conditions

Reaction Steps

A stirred solution of benzyl 6β-phenylacetamidobisnorpenicillanate (3.56 g, 8.9 mmol) in dry dichloromethane (15 ml) was cooled to -25° C. under nitrogen and treated with first, N-methylmorpholine (1.82 g, 1.97 ml, 17.98 mmol) and then, dropwise, with a solution of phosphorous pentachloride (2.25 g, 10.79 mmol) in dry dichloromethane (25 ml). The solution was stirred for 45 minutes during which time the temperature was allowed to reach 0° C. The mixture was then re-cooled to -25° C. and treated, dropwise, with dry methanol (40 ml, 0.9 mol). Stirring was continued for 21/2 hours at 0° C. when the contents of the reaction vessel were poured into iced water (140 ml). The pH of the mixture was adjusted to 2 with 5 N ammonium hydroxide solution (0.5 ml) and vigorous stirring continued for 20 minutes, at 0° C. The pH was then raised to 6 with 5 N ammonium hydroxide solution and the organic layer separated. The aqueous phase was re-extracted with dichloromethane (50 ml) and the combined organic fractions were washed with saturated sodium bicarbonate solution (15 ml), brine (2×20 ml), dried over anhydrous magnesium sulphate and evaporated to give an orange gum. This crude product was dissolved in ethyl acetate (25 ml), treated with a solution of p-toluene sulphonic acid monohydrate (1.7 g, 8.9 mmol) in acetone (3 ml) and stored at -5° C. for 1 hour. The precipitated solid was collected by filtration, washed with ethyl acetate (5 ml), ether (10 ml) and dried to give benzyl 6,β-aminobisnorpenicillanate, p-toluenesulphonic acid salt, as a colourless solid (1.93 g, 48%), m.p. 170°-172° dec. (lit., 169°-170°; Vanderhaeghe et al, J. Med. Chem., 1974, 17, 4, 389; 163°-165°; Osborne, J.C.S. Perkin I, 1980, 150), νmax (Nujol) 1790, 1750 cm-1 [Nujol is a registered trade mark], δ [acetone-d6 +DMSO-d6 ] 7.75 (2H, d, J 8 Hz), 7.45 (5H, s), 7.15 (2H, d, J 8 Hz), 5.50-5.10 (5H, m), 3.55 (2H, m) and 2.35 (3H, s) ppm.

Provenance & Evidence