Boron trifluoride → N-Methyldesloratadine

HRID 1606947Notes

Reaction equation

HRID 1606947 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]=1

Participants

4

Reactant 3

HCID 6356Boron trifluorideHCID 14917Hydrofluoric AcidHCID 13920590(3-(2-(3-Chlorophenyl)ethyl)-2-pyridinyl)(1-methyl-4-piperidinyl)methanone hydrochloride

Product 1

HCID 31843N-MethyldesloratadineYield 93.8%

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.

Workup

  1. customThe reaction was quenched
  2. extractionThe product was extracted into toluene which
  3. washwas washed with water and brine
  4. concentrationThe toluene solution was concentrated to a residue which
  5. customwas triturated with hot hexanes
  6. customInsoluble salts were removed by filtration
  7. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-1ddebf5c7b6e426f910d62aea8480326
Source dataset
uspto-grants-1989_09
Patent number
US04863931

Reaction notes

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