Nitric Acid → HCID 86724398, compound

Participants

Reaction Conditions

Reaction Steps

(4aS,5S,7aS)-5-(difluoromethyl)-7a-(2,3-difluorophenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine, obtained in Preparation Example 1-(9), (565 mg) was dissolved in TFA (3 mL), and the solution was cooled to 0° C. Sulfuric acid (conc., 0.8 mL) was added, followed by fuming nitric acid (0.08 mL) dropwise over 20 mins. After stirring at 0° C. for 90 min, the reaction mixture carefully neutralized with NaHCO3 (sat., aq., 50 mL) and extracted with EtOAc (3×100 mL), and the combined organic portions dried over MgSO4 and evaporated. The residue was purified by silica gel column chromatography (0% to 80% EtOAc in hexanes) to afford the title compound (700 mg, purity approx. 80%) which was used in the subsequent step without purification. 1H NMR (400 MHz, CDCl3) δ ppm 3.04 (dd, J=14.0, 3.9 Hz, 1H), 3.23-3.31 (m, 1H), 3.59 (d, J=3.0 Hz, 1H), 4.23 (d, J=9.9 Hz, 1H), 4.44-4.60 (m, 2H), 6.02 (t, J=57.6 Hz, 1H), 8.02-8.26 (m, 2H)

Provenance & Evidence