Chloroacetaldehyde → Ethyl 2-methyl-3-pyrrolecarboxylate

HRID 642401Notes

Reaction equation

HRID 642401 reaction equation
[OH-].[NH4+:2].Cl[CH2:4][CH:5]=O.[C:7]([O:13][CH2:14][CH3:15])(=[O:12])[CH2:8][C:9]([CH3:11])=O>>[CH2:14]([O:13][C:7]([C:8]1[CH:5]=[CH:4][NH:2][C:9]=1[CH3:11])=[O:12])[CH3:15]

Participants

4

Reactant 3

HCID 33ChloroacetaldehydeHCID 8868Ethyl AcetoacetateHCID 14923Ammonium Hydroxide

Product 1

HCID 136747Ethyl 2-methyl-3-pyrrolecarboxylateYield 33.4%

Procedure

Ammonium hydroxide (28 to 30% (HCl titration (as NH3)), 290 mL, 4.3 mol) was added dropwise to a mixture of chloroacetaldehyde (50% wt aqueous solution, 182 mL, 1.43 mol) and ethyl acetoacetate (183 mL, 1.43 mol) at 0° C. The ice bath was removed, and the reaction mixture was stirred at ambient temperature overnight. The reaction mixture was extracted twice with ethyl acetate. The combined organic layers were washed with 2N hydrochloric acid and saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified by flash chromatography eluting from silica gel with a gradient of 0-50% ethyl acetate in hexanes to afford 73.1 g of the title compound as a yellow solid. 1H NMR (200 MHz, CDCl3) δ 6.55 (2H, d, J=2.4 Hz), 4.26 (2H, q, J=7.4 Hz), 2.52 (3H, s), and 1.34 (3H, t, J=7.4 Hz).

Workup

  1. customThe ice bath was removed
  2. extractionThe reaction mixture was extracted twice with ethyl acetate
  3. washThe combined organic layers were washed with 2N hydrochloric acid and saturated sodium chloride aqueous solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography
  7. washeluting from silica gel with a gradient of 0-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-de9b2eb6a0694f5d85896da601be189d
Source dataset
uspto-grants-2010_04
Patent number
US07696223B2

Reaction notes

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