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US 9,708,284 B2Granted
Process for the preparation of olopatadine and sylil intermediates thereof
AssigneeLaboratorio Chimico Internazionale S.p.A.
InventorsPaolo Maria Farina, Renè Ignacio Rodriguez Curiel, Stefano Maiorana, Aldo Bianchi, Federica Colombo, Gabriele Timpano
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Abstract
The present invention refers to a new “one-pot” process for the preparation of olopatadine via intermediates of formula (III).
Claims14
A process for the preparation of olopatadine of formula (I)
- or a salt thereof, comprising protecting, by means of a silylating agent, isoxepac of formula (II)
- to give a silyl ester derivative thereof of formula (III)
- wherein R1, R2, R3 are selected from alkyl and phenyl, in an aprotic solvent;
- performing the Wittig reaction in the same reaction solution;
- cleaving the protecting group and obtaining olopatadine or a salt thereof, without isolating any intermediate compound.
2 more elements
A process for the preparation of olopatadine or a salt thereof, wherein:
- (a) reacting the compound of formula (II′)
- wherein R represents hydrogen or an alkali metal, with a silylating agent selected from, when R is hydrogen, a N,O-bis(trialkyl-silyl)acetamide, a N,O-bis(alkyl-diphenyl-silyl)acetamide, N,O-bis(triphenyl-silyl)acetamide and hexamethyldisilazane or, when R is an alkali metal, a (trialkyl-silyl)chloride, an (alkyl-diphenyl-silyl)chloride and (triphenyl-silyl)chloride, in an aprotic solvent;
- (b) adding 3-dimethylaminopropyltriphenylphosphonium bromide hydrobromide to the reaction mixture from step (a) and subsequently adding a strong base;
- (c) adding water into the solution from step (b) to cleave the silyl protecting group;
- and
- (d) isolating olopatadine and optionally transforming it into a salt thereof.
3 more elements
Dependencies are inferred from the claim text.