Dimethylformamide → 2-Formyl-3-(4-methylphenyl)pyrrole

HRID 493162Notes

Reaction equation

HRID 493162 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[CH:11][NH:10][CH:9]=2)=[CH:4][CH:3]=1.O=P(Cl)(Cl)Cl.CN([CH:21]=[O:22])C>C(Cl)Cl>[CH:21]([C:9]1[NH:10][CH:11]=[CH:12][C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=1)=[O:22]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 105349353-(4-Methylphenyl)pyrrole

Product 1

HCID 467385812-Formyl-3-(4-methylphenyl)pyrrole

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Following a standard procedure (Balasubramanian, T. et al., J. Org. Chem. 2000, 65, 7919-7929), a solution of 7 (472 mg, 3.00 mmol) in DMF (0.96 mL) and CH2Cl2 (30 mL) under argon was cooled to 0° C. and then POCl3 (340 μL, 3.60 mmol) was added dropwise. After 1 h, the flask was warmed to room temperature and stirred overnight (˜18 h). The reaction was quenched at 0° C. with 2.5 M NaOH (25 mL). The mixture was poured into water (50 mL), extracted with CH2Cl2, and the combined organic layers were washed with water, brine, dried (Na2SO4), and concentrated. The residue was chromatographed [silica, CH2Cl2/ethyl acetate (9:1)] to give a brown solid. 1H NMR spectroscopy showed two regioisomers in ˜13:1 ratio. Cooling of the solution (ethyl acetate/hexanes) at ˜−16° C. resulted in precipitation of an orange solid, which proved to be a single regioisomer (354 mg, 64%): mp 149-150° C.; 1H NMR δ 2.41 (s, 3H), 6.42-6.44 (m, 1H), 7.10-7.13 (m, 1H), 7.26 (d, J=8.0 Hz, 2H), 7.40 (d, J=8.0 Hz, 2H), 9.63-9.64 (m, 1H), 9.52-9.78 (br, 1H); 13C NMR δ 21.4, 111.6, 126.2, 128.9, 129.3, 129.7, 130.9, 137.7, 137.9, 180.2; FAB-MS obsd 186.0907, calcd 186.0919 (C12H11NO).

Workup

  1. customThe reaction was quenched at 0° C. with 2.5 M NaOH (25 mL)
  2. additionThe mixture was poured into water (50 mL)
  3. extractionextracted with CH2Cl2
  4. washthe combined organic layers were washed with water, brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was chromatographed [silica, CH2Cl2/ethyl acetate (9:1)]
  8. customto give a brown solid
  9. customresulted in precipitation of an orange solid, which

Sources & evidence

ORD record
ord-d43a9c3829334251a19b7a04d736ffc3
Source dataset
uspto-grants-2009_05
Patent number
US07534807B2

Reaction notes

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