1,4-bis-Boc-2-hydroxymethylpiperazine (13.9 kg) and 95% ethanol (30 kg) were added to the reactor, followed by the addition of an aqueous solution (water 21 kg) of configured sodium hydroxide (3.5 kg). The reaction mixture was then heated to reflux. Once the reaction was completed, ethanol was concentrated under reduced pressure. Subsequently, 30 kg of dichloromethane was added and the mixture was separated into liquid and aqueous phases. The aqueous phase was extracted three times with 3 × 20 kg of dichloromethane, and the organic phases were combined. The resulting solution was washed once with 40 kg of a 15% aqueous sodium chloride solution and dried with anhydrous sodium sulfate. Further purification was carried out to obtain (R)-1-BOC-3-(Hydroxymethyl)piperazine.
