(2R,5S)-4-Benzyl-2-methyl-5-(2-oxo-pyrrolidin-1-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester → (2R,5S)-2-Methyl-5-(2-oxo-pyrrolidin-1-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475434Notes

Reaction equation

HRID 1475434 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14][N:15]2[CH2:19][CH2:18][CH2:17][C:16]2=[O:20])[N:11](CC2C=CC=CC=2)[CH2:10][C@H:9]1[CH3:28])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)(=O)C.C(O)C.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14][N:15]2[CH2:19][CH2:18][CH2:17][C:16]2=[O:20])[NH:11][CH2:10][C@H:9]1[CH3:28])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 70980575(2R,5S)-4-Benzyl-2-methyl-5-(2-oxo-pyrrolidin-1-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 70981045(2R,5S)-2-Methyl-5-(2-oxo-pyrrolidin-1-ylmethyl)-piperazine-1-carboxylic acid tert-butyl esterYield 86%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 18476134Acetic acid ethanolSolvent

Procedure

(2R,5S)-4-Benzyl-2-methyl-5-(2-oxo-pyrrolidin-1-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (5.9 g, 15.25 mmol) and 10% Pd/C (2.13 g, 1.5 mmol) were dissolved in glacial acetic acid/ethanol (27.2 mL/72.6 mL) and stirred under hydrogen at 1 bar for 1 h. The mixture was filtered and the filtrate concentrated. Saturated aqueous sodium hydrogen carbonate and EtOAc were added. The EtOAc layer was separated and the aqueous phase extracted with DCM (3×). The combined DCM layers were dried with sodium sulfate, filtered and concentrated. The residue was azeotroped with toluene, to give the title compound (3.9 g), 1H NMR (CDCl3): 4.23-4.08 (1H, m), 3.95-3.77 (1H, m), 3.69 (1H, d), 3.59-3.46 (1H, m), 3.46-3.34 (1H, m), 3.34-3.07 (3H, m), 3.07-2.89 (1H, m), 2.55-2.39 (3H, m), 2.15-1.92 (2H, m), 1.48 (9H, s), 1.23 (3H, d).

Workup

  1. filtrationThe mixture was filtered
  2. concentrationthe filtrate concentrated
  3. additionSaturated aqueous sodium hydrogen carbonate and EtOAc were added
  4. customThe EtOAc layer was separated
  5. extractionthe aqueous phase extracted with DCM (3×)
  6. dry with materialThe combined DCM layers were dried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was azeotroped with toluene

Sources & evidence

ORD record
ord-2c0b756ad17b451d893942b02572d4b8
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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