Reaction Steps
A mixture of (3S-trans)-4-amino-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (0.65 g, 0.003 mol, from Example 1, part B) and [3-(1H-tetrazol-5-yl)phenylcarbamic acid, 4-nitrophenyl ester (1.08 g, 0.0033 mol, from part A) in acetonitrile (35 mL) and dimethylformamide (20 mL) was stirred at 80° C. for two hours. The reaction mixture was concentrated in vacuo and the residue, diluted with ethyl acetate, was washed with 0.5M HCl and water. The organic layer was concentrated in vacuo, and the residue was azeotroped with toluene and triturated with ethyl acetate/hexane (1:1). The product was purified by flash chromatography (EM-60 flash silica gel, 300 mL) and eluted with EtOAc/MeOH/HOAc (20:1:0.06). The solvent was removed in vacuo, acetic acid was azeotroped with toluene and the product was triturated in hexane (40 mL) and ethyl acetate (0.5 mL) and dried in vacuo to give 0.72 g (60%) of the title compound, m.p. 204°-208° C. TLC, silica gel, EtOAc/MeOH/HOAc (20:1:0.2), Rf =0.58; 1H-NMR (DMSO-d6) δ1.3 (s, 3H), 1.5 (s, 3H), 3.7 (d, J=9.4 Hz, 1H), 4.8 (dd, J=8.8 & 8,8 Hz, 1H), 5.8 (s, 1H), 6.8 (d, J=8.2 Hz, 1H), 7.0 (d, J=8.8 Hz, 1H), 7.5 (m, 5H), 8.4 (s, 1H), 9.0 (s, 1H); 13C-NMR (DMSO-d6) δ5 156.6, 156.0. 141.6, 132.9, 132.8, 130.2, 126.2, 125.0, 120.7, 120.1, 119.4, 118.2, 116.5, 103.0, 80.7, 71.6, 49.8, 26.9, 21.4, 19.3; IR (KBr) 2980, 2932, 2228, 1663 cm-1. M.S., (M+H)+ at 406, M.W. 405; [60 ]D=-41.6° (c=0.76 DMSO).
