(R)-4-BOC-1-CBZ-2-HYDROXYMETHYLPIPERAZINE Chemical Properties

Boiling point:

480.5±30.0 °C(Predicted)

Density 

1?+-.0.06 g/cm3(Predicted)

storage temp. 

2-8°C

pka

14.97±0.10(Predicted)

Appearance

Colorless to off-white Viscous liquid

(R)-4-BOC-1-CBZ-2-HYDROXYMETHYLPIPERAZINE Usage And Synthesis

Synthesis

General procedure for the synthesis of R-4-Boc-1-Cbz-2-hydroxymethylpiperazine from (R)-N-1-Boc-N-4-Cbz-2-piperazinecarboxylic acid: (2R)-4-[(phenylmethoxy)carbonyl]-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (1.4 g, 3.9 mmol) was dissolved in dimethoxyethane (10 mL), cooled, and N-methylmorpholine (0.4 g, 3.9 mmol) was added dropwise to the solution. N-methylmorpholine (0.4 g, 3.9 mmol) was added dropwise to the solution, followed by isobutyl chloroformate (0.54 g, 3.9 mmol). The reaction mixture was stirred at 0 °C for 20 min and then filtered. The filtrate was transferred to a 500 mL flask and cooled again. Sodium borohydride (0.22 g, 5.9 mmol) dissolved in water (5 mL) was added to the cooled filtrate and the external cooling bath was removed. The reaction mixture was stirred until its temperature rose to room temperature, then water (120 mL) was added. The mixture was extracted three times with ethyl acetate, the organic phases were combined, dried and the solvent evaporated. The product was purified by silica gel column chromatography (eluent: ethyl acetate/heptane, 10% to 70% gradient elution) to afford 1.2 g (84% yield) of 4-benzyl 1-tert-butyl (2R)-2-(hydroxymethyl)piperazine-1,4-dicarboxylate as a colorless oil.1H NMR (500 MHz, CDCl3): δ 1.4 (s, 9H), 2.7-3.2 (b , 4H), 3.5 (b, 2H), 3.8-4.2 (m, 4H), 5.1 (m, 2H), 7.2-7.4 (m, 5H); LCMS: m/z 349 (M-1).

References

[1] Patent: WO2007/37743, 2007, A1. Location in patent: Page/Page column 47