Sodium hydride (60% dispersion in mineral oil, 5.6 g, 0.140 mol) was added slowly to a solution of 6-methyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dione (68) (11.07 g, 0.060 mol) in anhydrous DMF stirred under argon at 0° C. The solution was stirred for 15 minutes before adding 3-fluoro benzylbromide (7.6 mL, 0.062 mol). The solution was allowed to come at room temperature and further stirred for 3 hours. The solution was cooled to −10° C. and diethylmalonate (9.36 mL, 0.061 mol) was added slowly. The solution was heated at 110° C. (TLC control). The reaction was cooled and poured into aqueous sodium carbonate (7.7 g, 0.072 mol) solution. The aqueous solution was washed with isopropyl ether and acidified to pH 2 with dil. HCl. The solids were filtered, washed by cold water and air dried to yield 16.9 g (97%) of 7-(3-fluoro-benzyl)-4-hydroxy-2-methyl-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester (69). 1H-NMR (DMSO-d6) δ 1.30 (t, J=7.2 Hz, 3H), 2.40 (d, J=1.2 Hz, 3H), 4.32 (q, J=7.2 Hz, 2H), 5.22 (s, 2H), 7.05-7.15 (m, 4H), 7.38 (m, 1H), 13.25 m/z 362 (M+1).
