Potassium Carbonate → Benzyl 4-(2-hydroxyethyl)-3-oxopiperazine-1-carboxylate

HRID 888940Notes

Reaction equation

HRID 888940 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][O:19]C(=O)C)[C:13](=[O:23])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+]>CO.O.C(Cl)(Cl)Cl>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][OH:19])[C:13](=[O:23])[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 2

HCID 11430Potassium CarbonateHCID 574203464-(2-Acetoxy-ethyl)-3-oxo-piperazine-1-carboxylic acid benzyl ester

Product 1

HCID 53766777Benzyl 4-(2-hydroxyethyl)-3-oxopiperazine-1-carboxylateYield 97.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

To 4-(2-acetoxy-ethyl)-3-oxo-piperazine-1-carboxylic acid benzyl ester (925 mg) in methanol (10 ml) was added potassium carbonate (800 mg) in water (4 mL). After 2 hours at room temperature the mixture was diluted with chloroform, washed with brine, dried (MgSO4) and the solvent removed in vacuo to yield 4-(2-hydroxy-ethyl)-3-oxo-piperazine-1-carboxylic acid benzyl ester (780 mg). This material was dissolved in ethanol and stirred over 10% Pd/C under an atmosphere of hydrogen for 24 hours. The reaction mixture was then filtered through celite and the solvent removed in vacuo to give 1-(2-hydroxy-ethyl)-piperazin-2-one (413 mg), which was used in a standard reductive amination procedure with 2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine-6-carbaldehyde to give 4-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-1-(2-hydroxy-ethyl)-piperazin-2-one. This compound (150 mg) was used in a Suzuki coupling with 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole (96 mg) to give after flash silica purification the title compound (39 mg) as a white solid.

Workup

  1. washwashed with brine
  2. dry with materialdried (MgSO4)
  3. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-74668a6403d94c7eb9a5b137e9d2e9d6
Source dataset
uspto-grants-2012_08
Patent number
US08252792B2

Reaction notes

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