Hydrogen Bromide → Citalopram Hydrobromide

Participants

Reaction Conditions

Reaction Steps

To a mixture 5.42 g sodium hydride in 120 ml of dimethylsulfoxide, previously heated at 60° C. for 30 minutes, under nitrogen flow, a solution of 30 g of 1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile obtained in Example 2 in 75 ml of dimethylsulfoxide is added, without exceeding 25° C. The solution is maintained under stirring for 30 minutes and, in 10 minutes, 33 g of 3-(dimethylamino)propylchloride are added without exceeding 25° C. After about 2-hour stirring at 25° C., the mixture is cooled at 10° C. and 300 ml of water are added dropwise and then 120 ml of ethyl acetate. The mixture is stirred and diluted with 1650 ml of water and 120 ml of ethyl acetate. The mixture is let 1 hour under stirring, then the phases are separated; the organic one is collected and the aqueous one is washed with 3×150 ml of ethyl acetate. After separation of the phases, the aqueous one is discarded and the collected organic ones are washed with 900 ml of water. The organic phase is dehydrated with anhydrous Na2SO4 and is concentrated under vacuum at 50° C. until an oil is obtained, which is treated with 60 ml of acetone. The mixture is stirred in order to obtain a solution, that is cooled at 10° C. and treated with about 10 ml of 48% HBr in order to adjust the pH value from 9.8-9.5 to 7.0. After 1 hour-stirring at pH=7 constant, the solvent is evaporated under vacuum at 50° C. and the residue is treated with 100 ml of acetone. The suspension is stirred at 25° C. for 30 minutes, then it is cooled at 0-5° C. and it is let at cold for 15 hours. The product is filtered, washed with cold acetone (0-5° C.) and is dried under vacuum at 50° C. Thus 34.88 g of citalopram hydrobromide with a purity (HPLC)=99.15% are obtained.

Provenance & Evidence