Tetrahydrofuran → di-tert-butyl (2S)-2-(((1-methylethyl)amino)methyl)-1,4-piperazinedicarboxylate

HRID 1972608Notes

Reaction equation

[CH3:1][CH:2]([NH:4][C:5]([C@H:7]1[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10][CH2:9][N:8]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=O)[CH3:3].B.C1COCC1.C1COCC1>CO>[CH3:3][CH:2]([NH:4][CH2:5][C@H:7]1[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:10][CH2:9][N:8]1[C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH3:1]

Participants

Conditions

Temperature: 50 °C

Procedure

A 500-mL round-bottomed flask was charged with di-tert-butyl (2R)-2-((1-methylethyl)carbamoyl)-1,4-piperazinedicarboxylate (1.77 g, 4.76 mmol, step 1), BH3.THF (1.0 M in THF, 15.0 mL, 15.0 mmol) and THF (60 mL). The mixture was heated at 50° C. for 12 h. After allowing the reaction to cool to room temperature, additional BH3.THF (1.0 M in THF, 5.0 mL, 5.0 mmol) was added. The mixture was then heated at 50° C. for 1.5 h. The reaction mixture was allowed to cool to room temperature and MeOH (20 mL) was slowly added. The solvent was removed in vacuo and the crude product was purified by column chromatography (100 g of silica gel, 0 to 10% iPrOH (with 10% NH4OH) in CHCl3) to afford di-tert-butyl (2S)-2-(((1-methylethyl)amino)methyl)-1,4-piperazinedicarboxylate (0.69 g) as a clear oil.

Workup

customthe reaction
temperatureto cool to room temperature
temperatureThe mixture was then heated at 50° C. for 1.5 h
temperatureto cool to room temperature
customThe solvent was removed in vacuo
customthe crude product was purified by column chromatography (100 g of silica gel, 0 to 10% iPrOH (with 10% NH4OH) in CHCl3)

Sources & evidence

ORD record: ord-f6c59a109b4344e794fd24dd4fdb365c
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431563B2

Reaction notes

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