Potassium Iodide → HCID 131726487, compound

Participants

Reaction Conditions

Reaction Steps

Into N,N-dimethylformamide (33.5 ml) were charged (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3-hydroxy-4-methylbenzyl)piperazine (6.7 g), potassium iodide (8.0 g), (2S)-4-(2-chloroethyl)-2-(methoxymethyl)morpholine hydrochloride (4.3 g) and N,N-diisopropylethylamine (4.8 g). The temperature was raised to 50 to 55° C. and allowed to react for 5 hours. After the reaction was completed, the reaction solution was cooled to room temperature. Ethyl acetate (33.5 ml) and water (33.5 ml) were added and mixed. After mixing was completed, layers were separated. The organic layer was washed by adding water (33.5 ml), layers were separated and the organic layer was concentrated. Ethyl acetate (33.5 ml) was added to the obtained oil of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[2-[(2S)-2-(methoxymethyl)-morpholino]ethyl]-2-(3-hydroxy-4-methylbenzyl)piperazine to effect dissolution and then the solution was concentrated. The obtained concentrate was diluted with acetone (100 ml), clarified and filtered, and washed with acetone (34 ml). Concentrated hydrochloric acid (3.9 g) was added dropwise to the combined filtrate and washings at room temperature and crystallization was effected under ice-cooling for 8 hours. Crystals were collected by filtration, washed with acetone (33.5 ml), dried under reduced pressure and moistured to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[2-[(2S)-2-(methoxymethyl)morpholino]ethyl]-2-(3-hydroxy-4-methyl-benzyl)piperazine dihydrochloride sesquihydrate (8.1 g, yield: 76.7%) in the form of white crystals.

Provenance & Evidence