p-Toluenesulfonic acid → 4-methoxybenzyl (2RS)-2-hydroxy-2-[(3R,4R)-4-mercapto-3-phenylacetamidoazetidin-2-on-1-yl]acetate

Participants

Reaction Steps

Toluene-4-sulphonic acid (3.42 g, 17.98 mmol) in water (8 ml) was added to a solution of 4-methoxybenzyl (2RS)-2-hydroxy-2-[(1R,5R)-3-benzyl-4-thia-2,6-diazabicyclo[3.2.0]hept-2-en-7-on-6-yl]acetate (4.12 g, 10.0 mmol) in dichloromethane (20 ml) and acetone (20 ml). After stirring for 2.5 h at room temperature, the reaction mixture was diluted with dichloromethane, washed with water (×2), dried and concentrated in vacuo to yield crude 4-methoxybenzyl (2RS)-2-hydroxy-2-[(3R,4R)-4-mercapto-3-phenylacetamidoazetidin-2-on-1-yl]acetate as a colourless foam. The crude thiol was dissolved in acetone (50 ml) and treated with a solution of 2-bromoacetyl-5-methyltetrahydrofuran (1.67 g, 8.1 mmol) in acetone (5 ml). After 10 min., potassium carbonate (687 mg, 5.0 mmol) was added, and the mixture stirred for a further 30 min. The reaction mixture was diluted with ethyl acetate, washed successively with water (×2) and brine, dried and concentrated. The residue was purified by chromatography on silica gel eluting with 50, 70 and 80% ethyl acetate in hexane to yield the title compound as a colourless foam (2.68 g, 60%); νmax (CH2Cl2) 3412, 1781, 1744, 1685 and 1515 cm-1. [Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MNa+ (579)].

Provenance & Evidence