Water → tert-butyl 4-[(2R)-3-benzyloxycarbonylamino-2-hydroxy-propyl]piperazine-1-carboxylate

HRID 2364707Notes

Reaction equation

HRID 2364707 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(N(C(C)C)CC)(C)C.[C:28](Cl)([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29].O>ClCCl>[CH2:31]([O:30][C:28]([NH:1][CH2:2][C@@H:3]([OH:18])[CH2:4][N:5]1[CH2:6][CH2:7][N:8]([C:11]([O-:13])=[O:12])[CH2:9][CH2:10]1)=[O:29])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[CH2:31]([O:30][C:28]([NH: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)=[O:29])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 7009319Tert-butyl 4-[(2R)-3-amino-2-hydroxy-propyl]piperazine-1-carboxylate

Product 2

HCID 68107180tert-butyl 4-[(2R)-3-benzyloxycarbonylamino-2-hydroxy-propyl]piperazine-1-carboxylateYield 52.6%HCID 1317313064-[(2R)-3-benzyloxycarbonylamino-2-hydroxy-propyl]piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The crude compound tert-butyl 4-[(2R)-3-amino-2-hydroxy-propyl]piperazine-1-carboxylate 20b (4.50 g, 17.40 mmol) was dissolved in 80 mL of dichloromethane in an ice-water bath followed by the addition of diisopropylethylamine (2.50 g, 19.10 mmol) and dropwise addition of 20 mL of a solution of carbobenzoxy chloride (2 g, 19.10 mmol) in dichloromethane successively, stirred for 12 hours. The resulting mixture was added with 20 mL of water and stirred for 10 minutes. 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×3), 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-[(2R)-3-benzyloxycarbonylamino-2-hydroxy-propyl]piperazine-1-carboxylate 20c (1.80 g, yield: 26.0%) as a light yellow oil.

Workup

  1. stirringstirred for 10 minutes
  2. concentrationThe reaction solution was concentrated under reduced pressure
  3. additionadded with 100 mL of water
  4. extractionextracted with ethyl acetate (100 mL×3)
  5. washThe combined organic phase was washed with saturated sodium chloride solution (50 mL×3)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6cac3d13c35d4c93905f1c540a43e3e8
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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