Water → (S)-Benzyl 3-(hydroxymethyl)piperazine-1-carboxylate

HRID 502524Notes

Reaction equation

HRID 502524 reaction equation
[NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][C@H:2]1[CH2:7][OH:8].[C:9](ON1C(=O)CCC1=O)([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10].O.C([O-])(O)=O.[Na+]>CC#N.CC(N(C)C)=O.O.CC(N(C)C)=O>[OH:8][CH2:7][C@H:2]1[NH:1][CH2:6][CH2:5][N:4]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:3]1

Participants

7

Reactant 4

HCID 962WaterHCID 83172Benzyl succinimido carbonateHCID 516892Sodium BicarbonateHCID 14288866[(2S)-piperazin-2-yl]methanol

Product 1

HCID 7023275(S)-Benzyl 3-(hydroxymethyl)piperazine-1-carboxylateYield 57.5%

Reagents, catalysts & solvents 2

HCID 31374DimethylacetamideSolventHCID 87231873CH3CN Dma H2OSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of compound 1B (207 mg, 1.78 mmol) in CH3CN/DMA/H2O (1 mL, 0.3 mL, 0.7 mL) cooled to 0° C. was added dropwise CBZ-OSu (444 mg, 1.78 mmol) in DMA (0.5 mL). The reaction was stirred for 15 min at 0° C. then slowly warmed to RT. To the reaction was added H2O (30 mL) and sat'd NaHCO3 (5 mL), and then the product was extracted three times with EtOAc (20 mL). The combined EtOAc layers were washed twice with brine, dried over MgSO4 then concentrated in vacuo to give crude (S)-benzyl 3-(hydroxymethyl)piperazine-1-carboxylate (256 mg). HPLC RT: 1.082 min (4 min Chromolith column TFA). (M+H)+:251.

Workup

  1. temperaturethen slowly warmed to RT
  2. extractionthe product was extracted three times with EtOAc (20 mL)
  3. washThe combined EtOAc layers were washed twice with brine
  4. dry with materialdried over MgSO4
  5. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-8a25b4d0aa2040a5a30cfd3f9ca0226e
Source dataset
uspto-grants-2010_08
Patent number
US07776859B2

Reaction notes

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