Reaction Steps
A suspension of (trans)-4-amino-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (prepared according to Evans et al., J. Med. Chem., 1983, 26, p. 1582 and J. Med. Chem., 1986, 29, p. 2194) (1.0 g, 4.6 mmol) in ethanol (4 ml) under argon was treated with phenylisocyanate (0.55 g, 4.6 mmol) and the reaction was heated at reflux temperature for 4 hours. The product precipitate out of the reaction. The reaction was then concentrated in vacuo and the residue was triturated with isopropylether to give the title compound as a colorless solid (0.9 g, 63%), m.p. 240-241° C.: 1H NMR (CDCl3 /DMSO) δ 8.3 (s, 1 H), 7.7 (s, 1 H), 7.4 (d, J=8.0 Hz, 3 H), 7.26 (t, J=8.0 Hz, 2 H), 7.0 (t, J=9.0 & 7.0 Hz, 1 H), 6.86 (d, J=9.0 Hz, 1 H), 6.4 (d, J=8.0 Hz, 1 H), 5.3 (d, J=5.0 Hz, 1 H), 4.9 (t, J=9.0 & 8.0 Hz, 1 H), 3.6 (dd, J=4.0 & 6.0 Hz, 1 H), 1.5 (s, 3 H), 1.3 (s, 3 H); 13C NMR (CDCl3 /DMSO) 157.0, 156.5, 139.1, 132.2, 132.1, 128.4, 123.9, 121.8, 118.2, 117.8, 80.0, 74.3, 49.9, 26.1, 18.4; IR (KBr) 1132, 1267, 1491, 1550, 1612, 1645, 2226, 2932, 2978, 3433 cm-1.
