Loratadine → Desloratadine

HRID 2244559Notes

Reaction equation

HRID 2244559 reaction equation
C(OC([N:6]1[CH2:11][CH2:10][C:9](=[C:12]2[C:18]3=[N:19][CH:20]=[CH:21][CH:22]=[C:17]3[CH2:16][CH2:15][C:14]3[CH:23]=[C:24]([Cl:27])[CH:25]=[CH:26][C:13]2=3)[CH2:8][CH2:7]1)=O)C.CS(O)(=O)=O>>[CH:21]1[CH:20]=[N:19][C:18]2[C:12]([C:13]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:14]=3[CH2:15][CH2:16][C:17]=2[CH:22]=1)=[C:9]1[CH2:10][CH2:11][NH:6][CH2:7][CH2:8]1

Participants

3

Reactant 2

HCID 3957LoratadineHCID 6395Methanesulfonic Acid

Product 1

HCID 124087DesloratadineYield 100.2%

Conditions

Temperature
107.5 °C

Procedure

A mixture of 4-(8-chloro-5,6-dihydrobenzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine-1-carboxylic acid ethyl ester (loratadine) (50.0 g, 0.13 mol), and 90% v/v aqueous methanesulfonic acid (165 ml) was heated to 105-110° C. for 9 hrs. The reaction mass was cooled to ambient temperature, quenched into water (300 ml) and the resulting solution heated at 90-100° C. for 1 hour. The reaction mixture was cooled to ambient temperature and extracted once with toluene (100 ml). The pH of the aqueous layer was adjusted between 4.0 to 5.0 with liquor ammonia and charcoalized (2.5 g decolorizing charcoal). The pH of the charcoalized solution was adjusted to >9.5 with liquor ammonia, and the sticky semi-solid mass which separated was extracted into toluene (300 ml). The toluene extract was concentrated under reduced pressure at below 65° C. and degassed to obtain an off-white to white solid of desloratadine (yield 40.5 g, purity >99.0%). HPLC analysis of the sample (as per the procedure described in example 2) did not show any peak due to impurity at relative retention time of 0.85 to 0.99 (relative to desloratadine peak).

Workup

  1. temperatureThe reaction mass was cooled to ambient temperature
  2. customquenched into water (300 ml)
  3. temperaturethe resulting solution heated at 90-100° C. for 1 hour
  4. temperatureThe reaction mixture was cooled to ambient temperature
  5. extractionextracted once with toluene (100 ml)
  6. customthe sticky semi-solid mass which separated
  7. extractionwas extracted into toluene (300 ml)
  8. extractionThe toluene extract
  9. concentrationwas concentrated under reduced pressure at below 65° C.
  10. customdegassed

Sources & evidence

ORD record
ord-443532e45fd7460093f0917522231c1a
Source dataset
uspto-grants-2010_03
Patent number
US07678908B2

Reaction notes

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