Ethyl 1H-pyrrole-2-carboxylate → HCID 57435098, compound

HRID 1434770Notes

Reaction equation

HRID 1434770 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][CH:8]=[CH:9][CH:10]=1)=[O:5])[CH3:2].[Cl-].[Al+3].[Cl-].[Cl-].[Br:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH2:22][C:23](Cl)=[O:24]>ClC(Cl)C>[CH2:1]([O:3][C:4]([C:6]1[NH:7][CH:8]=[C:9]([C:23](=[O:24])[CH2:22][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[Br:15])[CH:10]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 255670Ethyl 1H-pyrrole-2-carboxylateHCID 41383862-Bromophenylacetyl chlorideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 57435098HCID 57435098, compoundYield 54.9%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent2×

Procedure

Ethylpyrrole-2-carboxylate (1.9428 g, 13.96 mmol) in a minimal amount (5 mL) of dichloroethane was added to an ice cooled stirring mixture of aluminum chloride (4.0458 g, 30.34 mmol) and 2-bromophenylacetyl chloride (6.7116 g, 28.74 mmol) in dichloroethane (44 mL, 0.66 M) under N2. The ice bath was removed, and the reaction was stirred at room temperature for 2 h. 19.2977 g (2.6 mMol/g) Polyamine resin HL (200-400 mesh) and dichloroethane (20 mL) were added, and the reaction was stirred for ˜100 min. The reaction was then filtered through a glass-fritted funnel directly into ice water. The resin was rinsed with CH2Cl2, then the organic layers were removed, dried with Na2SO4, filtered, concentrated, and purified by silica gel chromatography (Combiflash column, 80:20 to 60:40 Hexanes:EtOAc) to obtain 2.5751 g (54.9%) 63 as a white solid. Note: A small amount of CH2Cl2 was required to solubilize the crude product before placement on the silica column. 1H (CDCl3, 400 MHz): δ 10.32 (1H, broad s), 7.57-7.53 (2H, m), 7.38-7.37 (1H, m), 7.29-7.21 (2H, m), 7.13-7.07 (1H, m), 4.35 (2H, q, J=7.2 Hz), 4.25 (2H, s), 1.36 (3H, t, J=7.2 Hz) ppm. 13C (CDCl3, 100 MHz): δ 191.78, 161.04, 134.91, 132.62, 131.66, 128.59, 127.40, 126.95, 126.25, 124.98, 124.17, 114.88, 60.92, 46.56, 14.26 ppm. DEPT (CDCl3, 100 MHz): CH3 carbons: 14.26; CH2 carbons: 60.92, 46.56; CH carbons: 132.62, 131.66, 128.59, 127.40, 126.95, 114.88 ppm. HPLC: 10.078 min.

Workup

  1. temperaturecooled
  2. customThe ice bath was removed
  3. stirringthe reaction was stirred at room temperature for 2 h
  4. addition19.2977 g (2.6 mMol/g) Polyamine resin HL (200-400 mesh) and dichloroethane (20 mL) were added
  5. stirringthe reaction was stirred for ˜100 min
  6. filtrationThe reaction was then filtered through a glass-fritted funnel directly into ice water
  7. washThe resin was rinsed with CH2Cl2
  8. customthe organic layers were removed
  9. dry with materialdried with Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. custompurified by silica gel chromatography (Combiflash column, 80:20 to 60:40 Hexanes:EtOAc)

Sources & evidence

ORD record
ord-bdea9ce1f9134b5b961935d8165e3330
Source dataset
uspto-grants-2009_11
Patent number
US07615572B2

Reaction notes

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