Yield:278788-66-2 91%

Reaction Conditions:

with lithium hydroxide monohydrate;sodium hydroxide in ethanol;Reflux;Large scale;

Steps:

1-2 Synthesis of compound 5 ((R)-1-Boc-3-hydroxymethylpiperazine):

Compound 4 (1,4-bis-Boc-2-hydroxymethylpiperazine) (13.9kg) and 95% ethanol 30kgAdd in the reactor, add the aqueous solution (water 21kg) of configured sodium hydroxide (3.5kg),Heating to reflux reaction, the reaction was completed, ethanol was concentrated under reduced pressure, after cooling, 30 kg of dichloromethane was added, and the liquid was separated. The aqueous phase was extracted three times with 3 × 20 kg of dichloromethane, and the organic phases were combined,It was washed once with 40 kg of 15% aqueous sodium chloride solution, and the organic phase was dried with anhydrous sodium sulfate.Concentrate to obtain crude oil, add 35kg of n-hexane to crystallize, filter,After drying, 8.6 kg of compound 5(R)-1-Boc-3-hydroxymethylpiperazine was obtained, with HPLC purity: 98.6%, yield: 91%.

References:

CN114349711,2022,A Location in patent:Paragraph 0024; 0032-0038