Sodium Carbonate → (S)-5,11-Dihydro-5-[2-(1-[4-methoxyphenethyl]-2-pyrrolidinyl)ethyl]dibenzo[b,e][1,4]thiazepine

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Reaction Steps

Potassium hydride (35% dispersion in oil, 110 mg) was added to a solution of 5,11-dihydrodibenzo[b,e][1,4]thiazepine (see Example 1) (570 mg) in DME (8 ml) and the mixture stirred at room temperature for 30 minutes, treated with a solution of (S)-2-(2-chloroethyl)-1-(4-methoxyphenethyl)pyrrolidine (480 mg) (prepared from the corresponding hydrochloride salt prepared in Preparation 4 by stirring a solution of the salt in dichloromethane with a slight excess of 10% aqueous sodium carbonate solution, separating the layers, drying the organic layer over sodium sulphate, and evaporating under reduced pressure to provide the desired free base) in DME (4 ml) and heated under reflux for two hours. The mixture was cooled to room temperature, quenched with water and extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulphate and evaporated under reduced pressure. The residue was purified by chromatography on silica gel, performing a gradient elution using initially dichloromethane/hexane (3:1) as eluant, changing to dichloromethane/methanol (97:3). The appropriate fractions were combined and evaporated under reduced pressure to give the title compound as a colourless oil, (460 mg, 58%).

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