Sodium hydride → 5-Oxo-4-prop-2-ynyl-piperazine-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester

HRID 1432923Notes

Reaction equation

HRID 1432923 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:27])[CH:6]([NH:16][C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])[CH2:7][N:8]([C:12](=[O:15])[CH2:13]Br)[CH2:9][C:10]#[CH:11]>C1COCC1>[CH3:3][O:4][C:5]([CH:6]1[CH2:7][N:8]([CH2:9][C:10]#[CH:11])[C:12](=[O:15])[CH2:13][N:16]1[C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])=[O:27]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 1317277242-Benzyloxycarbonylamino-3-(bromoactyl-prop-2-ynyl-amino)-propionic acid methyl ester

Product 1

HCID 539714095-Oxo-4-prop-2-ynyl-piperazine-1,2-dicarboxylic acid 1-benzyl ester 2-methyl esterYield 85.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (0.20 mg, 4.9 mmol) is added to a solution of 2-benzyloxycarbonylamino-3-(bromoactyl-prop-2-ynyl-amino)-propionic acid methyl ester (2.0 g, 4.8 mmol) in THF (50 mL) at 0° C. The solution is stirred for 40 minutes then quenched with saturated NH4Cl solution. The reaction mixture is concentrated in vacuo then diluted with CH2Cl2 and washed with brine. The organic layer is dried over, filtered and concentrated in vacuo. The crude product is purified by chromatography eluting with 50% EtOAc/hexanes to give the title product (1.4 g, 4.1 mmol). 1H NMR (CDCl3, 300 MHz) δ7.30 (m, 5H), 5.20 (s, 2H), 5.10 (m, 1H), 4.30 (dd, 1H), 4.25 (d, 2H), 4.08 (m, 1H), 4.00 (dd, 1H), 3.78 (dd, 1H), 3.78 (s, 3H), 2.25 (t, 1H).

Workup

  1. customthen quenched with saturated NH4Cl solution
  2. concentrationThe reaction mixture is concentrated in vacuo
  3. additionthen diluted with CH2Cl2
  4. washwashed with brine
  5. customThe organic layer is dried over,
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product is purified by chromatography
  9. washeluting with 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-c339b6c7d91e4f9ca6963726f1fbf4b8
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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