Hydrochloric Acid → (trans)-9-(3-bromo-4-fluorophenyl)-7-methyl-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione

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Reaction Conditions

Reaction Steps

The product from Example 84D (1.0 g, 2.5 mmol) was dissolved in chloroform (15 mL) under a nitrogen atmosphere, cooled to −10° C., treated with pyridine (0.24 mL, 3.0 mmol) and pyridinium tribromide (0.97 g, 3.0 mmol), stirred at −10° C. for 20 minutes, diluted with dichloromethane (100 mL) and treated with 1M HCl (10 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (50 mL). The combined organic layers were dried (MgSO4), filtered, concentrated, heated to 130° C. under nitrogen for 15 minutes and cooled to ambient temperature. The residue was purified by chromatography on silica gel eluting with 38:1:1:40 ethyl acetate:formic acid:water:hexane to provide the title compound as the faster moving diasteriomer which was crystallized from dichloromethane. 1H NMR (DMSO-d6) δ 1.22 (d, 3H), 4.12 (q, 1H), 4.48 (d, 1H), 4.65 (d, 1H), 4.68 (s, 1H), 4.86 (dd, 1H), 4.99 (d, 1H), 7.24-7.28 (m, 2H), 7.48 (dd, 1H), 10.42 (bs, 1H);

Provenance & Evidence