Methanol → (R)-1,4-(Di-Boc)-2-(hydroxymethyl)piperazine

HRID 1972691Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][C@@H:9]1[C:21](O)=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].B.C1COCC1.CO>C1COCC1>[OH:22][CH2:21][C@H:9]1[CH2:10][N:11]([C:14]([O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[O:15])[CH2:12][CH2:13][N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7]

Participants

Conditions

Temperature: 60 °C

Procedure

A 250-mL round bottom flask was charged with (2R)-1,4-bis(tert-butoxycarbonyl)-2-piperazinecarboxylic acid (10.5 g, 31.8 mmol, ASW Medchem, New Brunswick, N.J.) under nitrogen. THF (20 mL) was added and the mixture was cooled in an ice bath. A solution of BH3.THF (1M in THF, 65 mL, 65.0 mmol, Sigma-Aldrich) was added over 10 min. The ice bath was removed and after 15 min, the flask was equipped with a reflux condenser and was the reaction was heated at 60° C. After 1.5 h, the mixture was cooled in an ice bath and was then quenched with MeOH (10 mL, 247 mmol) over 20 min. The mixture was concentrated, treated with MeOH (20 mL), and concentrated a second time to give di-tert-butyl (2R)-2-(hydroxymethyl)-1,4-piperazinedicarboxylate as a white solid (10 g).

Workup

temperaturethe mixture was cooled in an ice bath
customThe ice bath was removed and after 15 min
customthe flask was equipped with a reflux condenser
temperaturethe mixture was cooled in an ice bath
concentrationThe mixture was concentrated
additiontreated with MeOH (20 mL)
concentrationconcentrated a second time

Sources & evidence

ORD record: ord-d0d524b72aed472abe660ffc08e49c32
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431563B2

Reaction notes

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