Sodium hydride → N-(4-Cyanobenzyl)-L-pyroglutamic acid methyl ester

HRID 55116

Reaction equation

HRID 55116 reaction equation
[CH3:1][O:2][C:3](=[O:10])[C@@H:4]1[CH2:8][CH2:7][C:6](=[O:9])[NH:5]1.[H-].[Na+].[C:13]([C:15]1[CH:22]=[CH:21][C:18]([CH2:19]Br)=[CH:17][CH:16]=1)#[N:14]>C1COCC1>[CH3:1][O:2][C:3](=[O:10])[C@@H:4]1[CH2:8][CH2:7][C:6](=[O:9])[N:5]1[CH2:19][C:18]1[CH:21]=[CH:22][C:15]([C:13]#[N:14])=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 78646Methyl 5-oxo-L-prolinateHCID 869964-(Bromomethyl)benzonitrile

Product 1

HCID 54410854N-(4-Cyanobenzyl)-L-pyroglutamic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

L-Pyroglutamic acid methyl ester (1.36 g, 0.0095 mol) was dissolved in dry THF (20 mL) under Ar, treated with NaH (60% oil dispersion) (0.58 g, 0.0145 mol) with stirring for 5 min, then the mixture was cooled to 0° C. p-Cyanobenzylbromide (1.78 g, 0.0091 mol) was added, and the mixture left to slowly warm to ambient temperature. After 48 h the reaction mixture was partitioned between EtOAc and satd NaHCO3 solution, the aqueous layer separated and washed with CH2Cl2, the organics combined, washed with brine and dried (MgSO4). Filtration and concentration to dryness followed by trituration with ether gave the white solid product. 1H NMR(CDCl3, 400 MHz) δ 7.62(2H, d, J=8 Hz), 7.33(2H, d, J=8 Hz), 4.98(1H, d, J=15.4 Hz), 4.13(1H, d, J=15.4 Hz), 3.99(1H, dd, J=3, 9 Hz) and 2.5-2.6 (1H, m), 2.4-2.5 (1H, m), 2.2-2.45 (1H, m), 2.1-2.2 (1H, m) ppm.

Workup

  1. additionwas added
  2. waitthe mixture left
  3. customAfter 48 h the reaction mixture was partitioned between EtOAc and satd NaHCO3 solution
  4. customthe aqueous layer separated
  5. washwashed with CH2Cl2
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationFiltration and concentration to dryness
  9. customgave the white solid product

Sources & evidence

ORD record
ord-d18623d16e6b413aa46d8681ce67e225
Source dataset
uspto-grants-1997_04
Patent number
US05624936

Linked notes

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