Reaction Steps
500 mg (1.1 mmol) of (3aRS, 4SR, 9SR, 9aRS)-4,9-ethano-2-(2-methoxyphenyl)acetyl-9-phenyl-2,3,3a,4,9,9a-hexahydro-1H-benzo[f]isoindole-3a-methanol are dissolved, at a temperature in the region of 20° C. under a nitrogen atmosphere, in 10 cm3 of pyridine which has been dried over potassium hydroxide and then 336 mg (1.2 mmol) of trifluoromethanesulphonic anhydride are added. After stirring for 3 hours at a temperature in the region of 20° C., 25 cm3 of water are added and extraction is carried out with 3 times 25 cm3 dichloromethane. The combined organic phases are washed with 0.1N hydrochloric acid and then with water, dried over magnesium sulphate and concentrated to dryness under reduced pressure. The residue is purified by recrystallizing from a methanol/isopropyl ether (60/40 by volume) mixture. 310 mg (42%) of N-[(3aRS, 4SR, 9SR, 9aRS)-4,9-ethano-2-(2-methoxyphenyl)acetyl-9-phenyl-2,3,3a,4,9,9a-hexahydro-1H-benzo[f]isoindolyl-3a-methyl]pyridinium trifluoromethanesulphonate are thus obtained in the form of pale-yellow crystals, the characteristics of which are as follows: melting point=244° C., 1H N.M.R. spectrum (250 MHz, d6-(CD3)2SO, at a temperature of 393 K, δ in ppm): 1.37, 1.67, 1.98 and 2.12 (4 mts, each 1H, CH2CH2), 2.80 (mt, 1H, H at 9a), 3.20 (mt, 1H, H at 4), 3.38 (limit AB, 2H, CH2 at 1), 3.52 (broad s, 2H, COCH2Ar), 3.56 at 4.02 (2 d, J=12.5 Hz, each 1H, CH2 at 3), 3.68 (unresolved peak, 3H, OCH3), 4.38 and 4.50 (2 d, J=12.5 Hz, each 1H, CH2N+), 6.51 (broad d, J=7.5 Hz, 1H, H at 8), 6.88 (broad t, J=7.5 Hz, 1H, aromatic H para to the OCH3), 6.95 (broad d, J=7.5 Hz, 1H, aromatic H ortho to OCH3), 7.15 (dt, J=7.5 and 2 Hz, 1H, H at 7), from 7.20 to 7.45 (mt, 4H, H at 5, H at 6 and aromatic H meta to the OCH3), from 7.35 to 7.60 (mt, 5H, aromatic H of the phenyl at 9), 8.15 (broad t, J=7 Hz, 2H, H at 3 and H at 5 of the pyridyl), 8.65 (broad t, J=7 Hz, 1H, H at 4 of the pyridyl), 8.91 (broad t, J=7 Hz, 2H, H at 2 and H at 6 of the pyridyl).
