Potassium Carbonate → Methyl 3-[(4-methyl-5-oxo-2-oxa-4-azabicyclo[4.4.0]deca-6,8,10-trien-9-yl)oxy]-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoate

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Reaction Steps

A mixture of methyl 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoate (Intermediate 8) (0.27 g, 1 mmol), 9-fluoro-4-methyl-2-oxa-4-azabicyclo[4.4.0]deca-6,8,10-trien-5-one (CAS no. 915771-24-3) (200 mg, 11 mol) and potassium carbonate (276 g, 2 mmol) in acetonitrile (20 mL) was heated in a microwave at 160° C. for 12 hours. The mixture was evaporated and the residue partitioned between ethyl acetate (40 mL) and water (40 mL). The organic phase was separated, washed with water (10 mL) and brine (20 mL), dried (MgSO4) and evaporated. The aqueous phase was acidified to pH 1 with 2N hydrochloric acid extracted with ethyl acetate (2×30 mL). The combined organic extracts were washed with water (2×20 mL), brine (20 mL), dried (MgSO4) and evaporated. The residue was dissolved in THF (2 mL) and methanol (1 mL) and treated with 2M TMS-diazomethane (0.14 mL) stirred for 30 minutes. The mixture was evaporated and the residue combined with that from the initial extraction and purified by flash chromatography on silica eluting with 0 to 100% ethyl acetate in isohexane to afford the product (232 mg, 54%). 1H NMR δ (300 MHz, CDCl3) 2.10-2.25 (m, 1H), 2.53-2.66 (m, 1H), 2.93 (s, 3H), 3.09 (s, 3H), 3.32-3.58 (m, 2H), 3.89 (s, 3H), 4.91 (t, 1H), 5.17 (s, 2H), 6.51 (s, 1H), 6.72 (d, 1H), 6.97 (s, 1H), 7.34 (s, 1H), 7.52 (s, 1H), 7.93 (d, 1H); m/z 427 (M+H+).

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