Water → HCID 69020955, compound

HRID 1865085Notes

Reaction equation

HRID 1865085 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:22])[C:8]([CH2:20][CH3:21])=[C:9]([C:18]#[N:19])[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)=[O:5])[CH3:2].[H-].[Na+].O>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:22])[C:8]([CH2:20][CH3:21])=[C:9]([C:18]#[N:19])[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:8][CH2:9][CH2:10][C:6]#[N:7])=[CH:13][CH:12]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 962WaterHCID 24758Sodium hydrideHCID 57974910HCID 57974910, compound

Product 1

HCID 69020955HCID 69020955, compoundYield 182.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Add dropwise, 4-cyano-5-ethyl-3-(4-hydroxyphenyl)-1-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (prepared in example E-81) (300 mg, 1.0 mmol) in DMF (10 mL) to a stirring solution of 60% sodium hydride (60 mg, 1.5 Eq.) in DMF (30 mL) at room temperature under a nitrogen atmosphere. After 30 minutes, add dropwise, 4-bromobutryonitrile (179 mg, 1.2Eq.) in DMF (10 mL) to the reaction mixture while continuing to stir at room temperature. After 2 hours, pour mixture into water and extract the desired ether into ethyl acetate. Wash the organic layer once with water, dry over potassium carbonate, filter, and concentrate under reduced vacuum to give 500 mg as an oil. Purify the material by silica gel chromatography (Chromatotron™) eluting with methylene chloride to provide 333 mg of the title compound as an oil. Mass spectrum (m/e): 366.2 (M*+1): (Bruker 300) 1H NMR δ (CDCl3) 7.27-7.32 (2H, d), 6.87-6.94 (2H , d) 4.03-4.16 (3H, m), 3.85-3.95 (3H, s), 2.78-2.88 (2H, dd), 2.54-2.64 (2H, t), 2.10-2.20 (2H, dd), 1.22-1.33 (4H, m), 1.00-1.10 (3H, t).

Workup

  1. additionAdd dropwise
  2. customat room temperature
  3. additionadd dropwise
  4. waitAfter 2 hours
  5. extractionextract the desired ether into ethyl acetate
  6. washWash the organic layer once with water
  7. dry with materialdry over potassium carbonate
  8. filtrationfilter
  9. concentrationconcentrate under reduced vacuum
  10. customto give 500 mg as an oil
  11. customPurify the material by silica gel chromatography (Chromatotron™)
  12. washeluting with methylene chloride

Sources & evidence

ORD record
ord-511f5dfaaee4478dbfc0dabf24977169
Source dataset
uspto-grants-2009_12
Patent number
US07625932B2

Reaction notes

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