Water → 2-(2-Nitroethyl)-3-(4-methylphenyl)pyrrole

HRID 1921562Notes

Reaction equation

HRID 1921562 reaction equation
[CH:1]([C:3]1[NH:4][CH:5]=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=1)=O.CC([O-])=[O:17].[K+].Cl.[CH3:21][NH2:22].[BH4-].[Na+].[OH2:25]>C(O)(=O)C.[N+](C)([O-])=O>[N+:22]([CH2:21][CH2:1][C:3]1[NH:4][CH:5]=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=1)([O-:17])=[O:25]

Participants

8

Reactant 5

HCID 962WaterHCID 517044Potassium AcetateHCID 4311764Sodium borohydrideHCID 6364545Methylamine hydrochlorideHCID 467385812-Formyl-3-(4-methylphenyl)pyrrole

Product 1

HCID 112069682-(2-Nitroethyl)-3-(4-methylphenyl)pyrroleYield 74%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6375NitromethaneSolvent

Procedure

A mixture of 8 (3.93 g, 21.2 mmol), KOAc (2.29 g, 23.3 mmol), methylamine hydrochloride (1.72 g, 25.4 mmol), and nitromethane (190 mL) under argon was stirred at room temperature. The mixture slowly became orange and yielded an orange-red precipitate. After stirring for 2.5 h, TLC showed the appearance of a new component and the disappearance of 8. The reaction was quenched with brine, extracted with ethyl acetate, and the organic layers were dried (Na2SO4) and concentrated. The residue was dissolved in THF/MeOH (210 mL, 3:7) at 0° C. NaBH4 (2.41 g, 63.6 mmol) was added in portions at 0° C. Then the mixture was stirred for 0.5 h at room temperature. The reaction mixture was neutralized with acetic acid (pH=7), then water (150 mL) was added and the mixture was extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried (Na2SO4), concentrated, and chromatographed [silica, hexanes/ethyl acetate (3:1)] to give a light brown solid (3.61 g, 74%): mp 81-82° C.; 1H NMR δ 2.37 (s, 3H), 3.44 (t, J=6.8 Hz, 2H), 4.54 (t, J=6.8 Hz, 2H), 6.27-6.29 (m, 1H), 6.73-6.75 (m, 1H), 7.20 (d, J=8.2 Hz, 2H), 7.23 (d, J=8.2 Hz, 2H), 8.19-8.36 (br, 1H); 13C NMR δ 21.2, 24.4, 75.2, 109.6, 117.7, 121.9, 123.2, 128.0, 129.5, 133.4, 135.8; FAB-MS obsd 230.1055, calcd 230.1055 (C13H14N2O2).

Workup

  1. customThe mixture slowly became orange and yielded an orange-red precipitate
  2. stirringAfter stirring for 2.5 h
  3. customThe reaction was quenched with brine
  4. extractionextracted with ethyl acetate
  5. dry with materialthe organic layers were dried (Na2SO4)
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in THF/MeOH (210 mL, 3:7) at 0° C
  8. stirringThen the mixture was stirred for 0.5 h at room temperature
  9. extractionthe mixture was extracted with ethyl acetate
  10. washThe combined organic layers were washed with water, brine
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated
  13. customchromatographed [silica, hexanes/ethyl acetate (3:1)]

Sources & evidence

ORD record
ord-599405f46ccd4e66921fa9ff7d3ed54e
Source dataset
uspto-grants-2012_05
Patent number
US08173691B2

Reaction notes

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