Nitric Acid → (4aS,5S,7aS)-7a-(2,3-difluoro-5-nitrophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine

Participants

Reaction Conditions

Reaction Steps

(4aS,5S,7aS)-7a-(2,3-Difluorophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine (1.42 g) was dissolved in TFA (6 mL), and the solution was cooled to 0° C. Sulfuric acid (conc., 1 mL) was added, followed by fuming nitric acid (0.30 mL) dropwise over 20 mins. After stirring at 0° C. for 1 h, the reaction mixture was poured onto ice (50 g) and basified to pH 12 with 2 N NaOH (aq.). After allowing the ice to melt, the mixture was extracted with EtOAc (3×75 mL), and the combined organic portions dried over MgSO4 and evaporated to afford the title compound (1.91 g, purity approx. 80%) which was used in the subsequent step without purification. 1H NMR (400 MHz, CDCl3) δ ppm 2.88 (dd, J=13.8, 3.9 Hz, 1 H), 3.11 (dd, J=13.6, 2.8 Hz, 1 H), 3.37 (dt, J=7.4, 3.5 Hz, 1 H), 3.93 (d, J=7.8 Hz, 1 H), 4.53-4.83 (m, 4 H), 8.09 (ddd, J=9.0, 6.3, 2.9 Hz, 1 H), 8.27 (dt, J=5.2, 2.6 Hz, 1 H)

Provenance & Evidence