Ethyl chloroformate → Loratadine

HRID 1606948Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1606948
Cl[C:2]([O:4][CH2:5][CH3:6])=[O:3].[Cl:7][C:8]1[CH:9]=[CH:10][C:11]2[C:21](=[C:22]3[CH2:27][CH2:26][N:25](C)[CH2:24][CH2:23]3)[C:16]3=[N:17][CH:18]=[CH:19][CH:20]=[C:15]3[CH2:14][CH2:13][C:12]=2[CH:29]=1>C1(C)C=CC=CC=1>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]2[C:21](=[C:22]3[CH2:23][CH2:24][N:25]([C:2]([O:4][CH2:5][CH3:6])=[O:3])[CH2:26][CH2:27]3)[C:16]3=[N:17][CH:18]=[CH:19][CH:20]=[C:15]3[CH2:14][CH2:13][C:12]=2[CH:29]=1

Komponenten

4

Edukt 2

HCID 10928Ethyl chloroformateHCID 31843N-Methyldesloratadine

Produkt 1

HCID 3957Loratadine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

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.

Aufarbeitung

  1. additionaddition
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. washthe toluene solution washed with water which
  4. concentrationThe organic layer was concentrated to a residue which
  5. dissolutionwas dissolved in hot acetonitrile
  6. concentrationThe solution was concentrated to a crystalline slurry which
  7. temperaturewas cooled (5° C)
  8. custombelow was isolated by filtration
  9. customyielding 42.4 g

Quellen und Nachweise

ORD-Eintrag
ord-ee051552dcb54af9abed84daa27d3613
Quelldatensatz
uspto-grants-1989_09
Patentnummer
US04863931

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