Dimethylformamide → Methyl 3-chloro-4-formyl-1H-pyrrole-2-carboxylate

HRID 1874956Notes

Reaction equation

HRID 1874956 reaction equation
CN([CH:4]=[O:5])C.O=P(Cl)(Cl)Cl.[Cl:11][C:12]1[CH:16]=[CH:15][NH:14][C:13]=1[C:17]([O:19][CH3:20])=[O:18]>ClC(Cl)C>[Cl:11][C:12]1[C:16]([CH:4]=[O:5])=[CH:15][NH:14][C:13]=1[C:17]([O:19][CH3:20])=[O:18].[Cl:11][C:12]1[CH:16]=[C:15]([CH:4]=[O:5])[NH:14][C:13]=1[C:17]([O:19][CH3:20])=[O:18]

Participants

6

Reactant 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 5324605Methyl 3-chloro-1H-pyrrole-2-carboxylate

Product 2

HCID 86644899Methyl 3-chloro-4-formyl-1H-pyrrole-2-carboxylateYield 27%HCID 86644900methyl 3-chloro-5-formyl-1H-pyrrole-2-carboxylateYield 27%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent2×

Procedure

DMF (0.579 mL, 1.48 mmol) was cooled to 0° C. under nitrogen. POCl3 (0.647 mL, 6.93 mmol) was added to the cold DMF and stirred at 0 oC, and a solid formed. Dichloroethane (2 mL) was added to the solid followed by the addition of methyl 3-chloro-1H-pyrrole-2-carboxylate (1.00 g, 6.26 mmol) in dichloroethane (2 mL). The reaction mixture was stirred for 10 minutes at 0° C. and heated to reflux until the starting material was no longer evident by TLC. The reaction mixture was cooled and partitioned between EtOAc and water. The organic layer was separated, washed with saturated NaHCO3, dried over MgSO4, filtered and the EtOAc evaporated. Purification was accomplished by silica gel column chromatography (0-30% EtOAc/hexanes) to afford the title compound (0.319 g, 27%), and methyl 3-chloro-5-formyl-1H-pyrrole-2-carboxylate (0.320 g, 27%). 1H NMR (400 MHz, Acetone-d6) δ ppm 11.83 (br. s., 1H), 9.89 (s, 1H), 7.72 (s, 1H), 3.86 (s, 3H). LCMS: m/z=188.2 (M+1).

Workup

  1. customa solid formed
  2. stirringThe reaction mixture was stirred for 10 minutes at 0° C.
  3. temperatureheated
  4. temperatureto reflux until the starting material
  5. temperatureThe reaction mixture was cooled
  6. custompartitioned between EtOAc and water
  7. customThe organic layer was separated
  8. washwashed with saturated NaHCO3
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customthe EtOAc evaporated
  12. customPurification

Sources & evidence

ORD record
ord-2dd96e61a9a140d984c888e07a05860b
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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