Ethyl chloroformate → Loratadine

Participants

Reaction Conditions

Reaction Steps

Ethyl chloroformate (40.4 mL; 45.9 g; 0.423 mol) was added slowly to a hot (-80° C) toluene solution (320 mL) of the 8-chloro-6,11-dihydro-11-(1-methyl-4-piperidinylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (45.7 g; 0.141 mol) from Example 1E containing the two corresponding fluoro-substituted compounds of the invention. Following complete addition, the temperature was maintained at 80° C. for 1 h. The reaction mixture was cooled to ambient temperature and the toluene solution washed with water which was adjusted to pH 10 with aqueous sodium hydroxide. The organic layer was concentrated to a residue which was dissolved in hot acetonitrile and decolorized with charcoal. The solution was concentrated to a crystalline slurry which was cooled (5° C). 8-chloro-6,11-dihydro-11-(1-ethoxycarbonyl-4-piperidylidene)-5H-benzo[5,6]cyclohepta [1,2-b]pyridine containing the two corresponding fluoro-substituted compounds of the invention as discussed in Examples 1G below was isolated by filtration yielding 42.4 g: m.p. 134.5°-136° C.; NMR (400 MHz, CDCl3)δ1.25 (t,3H,J=8 Hz), 2.3-2.4 (m,3H), 2.4-2.5 (m,1H), 2.7-2.9 (m,2H), 3.1-3.2 (m,2H), 3.3-3.4 (m,2H), 3.81 (br s, 2H), 4.13 (q,2H,J=8 Hz), 7.1-7.3 (m,4H), 7.43 (dd,1H,J=9,2 Hz), 8.40 (d,1H,J=5 Hz); mass spectrum, m/e (relative intensity) 385M+3 (35), 383 M+1 (100). Anal. Calcd. for C22H23N2ClO2 : C,69.00; H,6.05; N,7.32; Cl9.26. Found: C,69.37; H,6.09; N,7.35; Cl 9.37.

Provenance & Evidence