Methyl p-toluenesulfonate → HCID 86586537, compound

Participants

Reaction Steps

To 2.2 g (5.8 mmole) of toluene-4-sulfonic acid (2R)-8-amino-7-nitro-2,3-dihydro-benzo(1,4)dioxin-2-ylmethyl ester in 100 mL of methylene chloride was added 1.3 g (10 mmole) of N,N-diisopropylethylamine, followed by 2.1 g (10 mmole) of trifluoroacetic anhydride. The mixture was stirred at room temperature for 2 hours, then washed with 100 mL portions of 2 N HCl (aq) and water, dried over sodium sulfate, filtered through silica gel, using additional methylene chloride to fully elute the product, and concentrated in vacuum to 2.6 g (5.4 mmole) of the trifluoroacetamide. This was dissolved in 50 mL of N,N-dimethylformamide and 1.2 g (6.5 mmole) of methyl tosylate and 3.0 g (22 mmole) of potassium carbonate added. The mixture was heated at 50-60° C. under nitrogen for 15 hours. After the mixture had cooled, it was diluted to 300 mL with ethyl acetate and washed with 300 mL of water. The aqueous phase was back-extracted with 200 mL of ethyl acetate and the combined organics were washed with 250 mL portions of water and saturated brine, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was dissolved in 300 mL of methanol and 5.0 g (36 mmole) of potassium carbonate added. This mixture was stirred at room temperature for 24 hours, then filtered and concentrated in vacuum. The residue was column chromatographed on silica gel with methylene chloride as eluant to give 0.80 g of the (R)-enantiomer of the title compound as a yellow solid, m.p. 149-151° C.

Provenance & Evidence