Nitric Acid → HCID 68173882, compound

Participants

Reaction Conditions

Reaction Steps

(4aS,5S,7aS)-5-(fluoromethyl)-7a-(2-fluorophenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine (45.85 g, 161.26 mmol) was dissolved in TFA (192 mL), and the solution was cooled to 0° C. Sulfuric acid (conc., 33.65 mL, 161.26 mmol) was added, followed by fuming nitric acid (7.78 mL, 185.44 mmol) dropwise over 25 mins. After stirring at 0° C. for 30 mins, the reaction mixture was poured onto ice (500 g)/CHCl3 (500 mL) and basified to pH 12 with 6N NaOH (aq.). The two layers were separated and the aqueous layer was extracted with CHCl3 (2×500 mL). The combined organic extracts were dried over MgSO4 and concentrated to give the product as a light orange foam (52.11 g, 98%). 1H NMR (400 MHz, CDCl3) δ ppm 2.80 (dd, J=13.26, 3.92 Hz, 1H) 3.03 (dt, J=7.77, 3.82 Hz, 1H) 3.08 (dd, J=13.39, 3.28 Hz, 1H) 3.85 (dd, J=8.84, 2.27 Hz, 1H) 4.49-4.67 (m, 4H) 7.22 (dd, J=10.99, 8.97 Hz, 1H) 8.16-8.23 (m, 1H) 8.43 (dd, J=6.82, 2.78 Hz, 1H).

Provenance & Evidence