ChemicalBook CAS DataBase List (E)-Olopatadine Hydrochloride

(E)-Olopatadine Hydrochloride synthesis

10synthesis methods

Product Name:(E)-Olopatadine Hydrochloride
CAS Number:949141-22-4
Molecular formula:C21H24ClNO3
Molecular Weight:373.8732

Ethanamine, N-[(3,5-dichlorophenyl)methylene]-2,2-diethoxy-

1000210-73-0
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27710-82-3 Synthesis

[3-(Dimethylamino)propyl]triphenylphosphonium bromide hydrobromide

27710-82-3
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949141-22-4
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140462-76-6
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Yield: 99% ， 0.5%

Reaction Conditions:

Stage #1:anhydrous 3-(dimethylamino)propyltriphenylphosphonium bromide hydrobromide with sodium hydride in tetrahydrofuran for 3 h;Heating / reflux;Wittig Reaction;
Stage #2:(11-oxo-6,11-dihydro-dibenzo[b,e]oxepin-2-yl)-acetic acid benzyl ester in tetrahydrofuran at 0 - 30; for 3 h;
Stage #3: with hydrogenchloride;water in di-isopropyl ether; pH=2

Steps:

Charged 238 gms [3 - (Dimethylamino) propylamine] triphenyl phosphonium bromide hydrobromide in 1400 ml tetrahydrofuran under nitrogen atmosphere. Slowly charged 130.5 gms sodium hydride and raised the temperature to reflux to maintain for 3.0 hrs. The suspension cooled and chilled to 0⁰C and charged solution of 100 gms benzyl ester of 1 1 - oxo - 6, 1 1 - Dihydrodibenz [b, e] oxepin - 2 - acetic acid in 400 ml tetrahydrofuran and stirred the reaction mass at 25 - 30⁰C for 3.0 hours. Cooled the reaction mass to -10 to 5⁰C and quenched in 1700 ml water. The organic layer separated and washed with water. Combined aqueous layer washed with diisopropyl ether and acidified with dilute hydrochloric acid to pH 2. The acidified aqueous layer extracted with dichloromethane 2500 ml. The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue was taken in the mixture of 500 ml dichloromethane and diethyl ether solvent. The product was filtered and dried. The HPLC purity of the product Olopatadine hydrochloride obtained; Cis / Z Isomer = > 99.0%; Trans / E Isomer = < 0.5%.

References:

INDOCO REMEDIES LIMITED WO2009/81417, 2009, A2 Location in patent:Page/Page column 11-12