4-Fluorobenzyl bromide → 1-(4-fluoro-benzyl)-6-methyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dione

Participants

Reaction Conditions

Reaction Steps

step 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.

Provenance & Evidence