Benzyl Bromide → Methyl 1-benzyl-1H-pyrrole-2-carboxylate

HRID 1363306Notes

Reaction equation

HRID 1363306 reaction equation
[CH3:1][O:2][C:3]([C:5]1[NH:6][CH:7]=[CH:8][CH:9]=1)=[O:4].[H-].[Na+].[CH2:12](Br)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>CN(C=O)C>[CH2:12]([N:6]1[CH:7]=[CH:8][CH:9]=[C:5]1[C:3]([O:2][CH3:1])=[O:4])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 136930Methyl pyrrole-2-carboxylate

Product 1

HCID 21766231Methyl 1-benzyl-1H-pyrrole-2-carboxylateYield 56.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cooled (0° C.) solution of methyl-2-pyrrole carboxylate (8.00 g, 63.9 mmol) in DMF (320 mL) was added NaH (60% by weight 5.10 g, 128 mmol). After 20 min, benzylbromide (11.4 mL, 95.9 mmol) was added and the reaction was warmed to rt. Stirring was continued for 2 h before quenching with saturated aq NH4Cl (0.5 L). The mixture was extracted 3× with EtOAc and the combined organic layers were washed with H2O (3×) and brine, dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. The crude product was chromatographed over silica gel (0 to 10% EtOAc in heptane over 25 min) to give methyl 1-benzyl-1H-pyrrole-2-carboxylate as a colorless oil (7.75 g, 56%). Rf=0.48 (25:75 heptane/EtOAc); 1H NMR (400 MHz, CDCl3) δ (ppm) 7.28-7.34 (m, 2H) 7.23-7.27 (m, 1H) 7.09-7.13 (m, 2H) 7.01 (dd, J=4.0, 1.8 Hz, 1H) 6.88-6.91 (m, 1H) 6.19 (dd, J=4.0, 2.6 Hz, 1H) 5.57 (s, 2H).

Workup

  1. waitwas continued for 2 h
  2. custombefore quenching with saturated aq NH4Cl (0.5 L)
  3. extractionThe mixture was extracted 3× with EtOAc
  4. washthe combined organic layers were washed with H2O (3×) and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a yellow oil
  9. customThe crude product was chromatographed over silica gel (0 to 10% EtOAc in heptane over 25 min)

Sources & evidence

ORD record
ord-34a87f22fb4246f2815f932a53a233cd
Source dataset
uspto-grants-2011_02
Patent number
US07884124B2

Reaction notes

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