Benzyl Bromide → tert-butyl 4-[(2S)-3-(dibenzylamino)-2-hydroxy-propyl]piperazine-1-carboxylate

HRID 2364740Notes

Reaction equation

HRID 2364740 reaction equation
[NH2:1][CH2:2][C@H:3]([OH:18])[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1.C(=O)([O-])[O-].[K+].[K+].[CH2:25](Br)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C(O)C.O>[CH2:25]([N:1]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:2][C@H:3]([OH:18])[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:12])[CH2:7][CH2:6]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 7144880tert-butyl 4-[(2S)-3-amino-2-hydroxy-propyl]piperazine-1-carboxylate

Product 1

HCID 68107746tert-butyl 4-[(2S)-3-(dibenzylamino)-2-hydroxy-propyl]piperazine-1-carboxylateYield 43%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

Tert-butyl 4-[(2S)-3-amino-2-hydroxy-propyl]piperazine-1-carboxylate 7c (5 g, 19.30 mmol), potassium carbonate (10.70 g, 77.20 mmol) and benzyl bromide (7.90 g, 46.30 mmol) were dissolved in 120 mL of the mixture solvent of ethanol and water (V/V=5:1). The reaction solution was heated to 60° C. and stirred for 2 hours. The reaction solution was concentrated under reduced pressure, added with 100 mL of water and extracted with ethyl acetate (100 mL×3). The combined organic phase was washed with saturated sodium chloride solution (50 mL), then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound tert-butyl 4-[(2S)-3-(dibenzylamino)-2-hydroxy-propyl]piperazine-1-carboxylate 35a (3.65 g, yield: 43.0%) as a light yellow oil.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. additionadded with 100 mL of water
  3. extractionextracted with ethyl acetate (100 mL×3)
  4. washThe combined organic phase was washed with saturated sodium chloride solution (50 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-c660d6f750da4dc6a66f1ea288b3a0af
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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