[CH3:1][C:2]1[S:12][C:5]2[NH:6][C:7](=[O:11])[O:8][C:9](=[O:10])[C:4]=2[CH:3]=1.Br[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1>CN(C=O)C>[F:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][N:6]2[C:5]3[S:12][C:2]([CH3:1])=[CH:3][C:4]=3[C:9](=[O:10])[O:8][C:7]2=[O:11])=[CH:16][CH:17]=1step 3—Sodium hydride (1.5 g of a 60% dispersion in mineral oil, 37.5 mmol) was suspended in DMF (50 mL) in a 250 mL round-bottom flask equipped with a stir bar, and cooled to 0° C. and maintained under a nitrogen atmosphere. A solution of 61a (4.6 g, 25 mmol) dissolved in DMF (50 mL) was added dropwise through a septum. The flask was removed from the ice bath and the mixture was stirred at RT for 30 m. The reaction was cooled to 10° C. and 1-bromomethyl-4-fluoro-benzene (3.74 mL, 30 mmol) was added through the septum. The flask was removed from the ice bath and the mixture was stirred at RT for 2 h. The reaction was poured into ice and 1N HCl, extracted twice with EtOAc, dried (Na2SO4), filtered and concentrated. A solid was precipitated from the EtOAc by addition of Et2O and hexanes to afford 3.0 g (41%) of 1-(4-fluoro-benzyl)-6-methyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dione (61b): ms 2[M+Na]=605.
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