Reaction Steps
A solution of tert-butyl ((4aS,7aS)-7a-(5-amino-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate (Step D, Preparation 3, 32 mg, 0.087 mmol), cyclopentanone (23.38 μL, 0.261 mmol), sodium triacetoxyborohydride (55.4 mg, 0.261 mmol) and acetic acid (14.96 μL, 0.261 mmol) in THF (435 μL) was stirred at rt for 12 h, and LC/MS showed a very clean reaction. The crude reaction mixture was purified by reverse phase preparative HPLC on a Luna C18 column (10 μM, 30×100 mm) eluting with 0-100% B (A: 95% eater/5% MeCN/10 nM NH4OAc, B: 5% water/95% MeCN/10 mM NH4OAc) over 12 min to give tert-butyl ((4aS,7aS)-7a-(5-(cyclopentylamino)-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate (16 mg, 0.037 mmol, 42.2% yield) as a white solid. 1H NMR (500 MHz, CHLOROFORM-d) δ 6.90 (dd, J=11.1, 8.7 Hz, 1H), 6.74 (dd, J=6.4, 2.9 Hz, 1H), 6.51 (dt, J=8.7, 3.3 Hz, 1H), 4.22-4.14 (m, 1H), 4.04 (q, J=7.9 Hz, 1H), 3.74 (quin, J=6.1 Hz, 1H), 3.31 (dd, J=13.3, 3.1 Hz, 1H), 3.03 (br. s., 1H), 2.84 (dd, J=13.4, 4.3 Hz, 1H), 2.47-2.31 (m, 1H), 2.25-2.15 (m, 1H), 2.09-1.97 (m, 2H), 1.80-1.57 (m, 4H), 1.53-1.43 (m, 2H), and 1.50 (9H, s). MS (M+H)+: 436.3.
