Methanol → (2R,3S,5R,6R)6-Amino-2-carbamoyloxymethyl-2-methylpenam-3-carboxylic Acid p-Nitrobenzyl Ester

Participants

Reaction Steps

A solution of (2R,3S,5R,6R)2-(N-acetyl)carbamoyloxymethyl-2-methyl-6-phenoxyacetamidopenam-3-carboxylic acid p-nitrobenzyl ester (1.17 g, 2.0 mmol) in methylene chloride (10 ml) at -40° was charged with dimethylaniline (1.03 ml, 8.0 mmol) and phosphorous pentachloride (0.92 g, 4.4 mmol). The solution was stirred at -35° to -40° for 30 minutes and cold (~-35°) methanol (4.1 ml, 100 mmol) was added dropwise. The pale green solution was stirred at -35° to -40° for 2 hours and then quenched into ice-water (10 ml). The pH was adjusted to 1.7 with conc. ammonia and the layers were separated. The aqueous was washed with CH2Cl2 (5 ml), combined with a water back-extract (5 ml), and stirred with CH2Cl2 (10 ml) during pH adjustment to 6.5 with ammonia. The organic phase was withdrawn, washed (5 ml, H2O), combined with a back-extract (CH2Cl2, 10 ml), dried (4A sieves), filtered, concentrated to 4 ml and diluted with heptane (10 ml). The suspension was concentrated to 8 ml and the liquids were decanted. The solids were treated with CH2Cl2 (4 ml) and heptane (10 ml) in the same fashion, and the product was washed with heptane and dried to an off-white solid (0.28 g) 34%; nmr 100 MHz CDCl3 --D2O δ 8.24 (2, d, J=8.5 Hz, 1/2 pNB AB), 7.56 (2, d, J=8.5, pNB AB), 5.68 (1, brd J=4, C5 --H), 5.32 (2, s, benzyl CH2), 4.76 (1, s, C3 --H) 4.55 (HOD overlapping C6 --H d), 4.16 and 3.97 (2, ABq J=11.5 C2 --CH2 --O), 1.43 (3, s, C3 --CH3), with 2.36 (3/4, s, ##STR78## of impurity N-acetyl analog; ~25 mol %).

Provenance & Evidence