Loratadine → Desloratadine

HRID 2244558Notes

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>S(=O)(=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

Conditions

Temperature: 102.5 °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) (100.0 g, 0.26 mol), and 50% aqueous sulfuric acid (300 ml) was heated to 100-105° C. for 3 hrs. The reaction mass was cooled to ambient temperature and quenched into ice cold water (300 ml). The pH of the quenched mass was adjusted to pH 4.0 to 5.0 with liquor ammonia and charcoalized (5 g decolorizing charcoal). The pH of the charcoalized solution was adjusted to >9.5 with liquor ammonia, and sticky semi-solid mass which separated was extracted into toluene (700 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 78.0 g, 96%, 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

temperatureThe reaction mass was cooled to ambient temperature
customquenched into ice cold water (300 ml)
customseparated
extractionwas extracted into toluene (700 ml)
extractionThe toluene extract
concentrationwas concentrated under reduced pressure at below 65° C.
customdegassed

Sources & evidence

ORD record: ord-f314cdf7031c4592aa09ac4b9dfa997a
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07678908B2

Reaction notes

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