Boron trifluoride → N-Methyldesloratadine
Reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([CH2:9][CH2:10][C:11]2[C:12]([C:17]([CH:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)=O)=[N:13][CH:14]=[CH:15][CH:16]=2)[CH:6]=[CH:7][CH:8]=1.F.B(F)(F)F>>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]2[C:17](=[C:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[CH2:10][CH2:9][C:5]=2[CH:4]=1Participants
4
Procedure
To a solution of [3-[2-(3-chlorophenyl)ethyl]-2-pyridinyl]-1-methyl-4-piperidinyl methanone hydrochloride (59.0 g; 0.15 mol) in 120 mL (120 g; 6.0 mol) of hydrofluoric acid at -35° C. was added boron trifluoride (44.3 g; 0.66 mol) over 1 h. The reaction was quenched using ice water and potassium hydroxide to a final pH of 10. The product was extracted into toluene which was washed with water and brine. The toluene solution was concentrated to a residue which was triturated with hot hexanes. Insoluble salts were removed by filtration and the filtrate was concentrated to give as a main product 45.7 g (HPLC purity 96%, yield 91%) of 8-chloro-6,11-dihydro- 11-(1-methyl-4-piperidinylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine as an off-white solid: mp 116°-119° C.; NMR (200 MHz, CDCl3)δ2.0-2.2 (m,2H), 2.27 (s,3H), 2.3-2.6 (m,4H), 2.6-3.0 (m,4H), 3.3-3.6 (m,2H), 7.0-7.2 (m,4H), 7.44 (dd,1H,J=8, 2 Hz), 8.42 (dd,1H,J=3, 2 Hz); mass spectrum, m/e (rel intensity) 327M+3 (28), 325M+1 (100) Anal. Calcd. for C20H21N2Cl: C,73.94; H,6.52; N,8.63; Cl,10.92. Found: C,73.88; H,6.48; N,8.69; Cl10.80. This material was found to include the two corresponding fluoro-substituted compound of the invention as discussed further below.