Tetrahydrofuran → HCID 57659272, compound

HRID 2172846Notes

Reaction equation

HRID 2172846 reaction equation
Br.Br[CH:3]([CH3:12])[C:4]([C:6]1[CH:11]=[CH:10][N:9]=[CH:8][CH:7]=1)=O.N1[CH:18]=[CH:17][C:16]([C:19]2[NH:20]C(C3C=CN=CC=3)=C[C:23]=2[C:24]([OH:26])=[O:25])=[CH:15][CH:14]=1.[H-].[Na+].[C:35]([O-])(=O)[CH3:36].[NH4+].[CH2:40]1COCC1>>[CH2:35]([O:26][C:24]([C:23]1[C:3]([CH3:12])=[C:4]([C:6]2[CH:11]=[CH:10][N:9]=[CH:8][CH:7]=2)[NH:20][C:19]=1[C:16]1[CH:15]=[CH:14][CH:40]=[CH:18][CH:17]=1)=[O:25])[CH3:36]

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 517165Ammonium AcetateHCID 18470777HCID 18470777, compoundHCID 85792903HCID 85792903, compound

Product 1

HCID 57659272HCID 57659272, compoundYield 36%

Conditions

Temperature
50 °C

Procedure

2-Bromo-1-pyridin-4-yl-propan-1-one hydrobromide 46 (0.6 g, 2 mmol) was added to a mixture of 3-oxo-3-phenyl-propionic acid ethyl ester 2 (R=H, 0.3 g, 1.56 mmol) in 300 mL of dry THF and NaH (0.18 g) at 0° C. The solution was left at 0° C. for 1 h and then stirred at 50° C. for 4 h. The solvent was removed and the residue was dissolved in 20 mL of EtOH, ammonium acetate (0.7 g, 9.3 mmol) was added and the reaction mixture was left overnight at rt. The reaction mixture was concentrated, water was added and the slurry extracted with EtOAc. The combined organic layers were washed with water, dried (Na2SO4), filtered and concentrated. The crude was purified by flash chromatography (DCM/MeOH 95:5) affording 170 mg (36%) of 4-methyl-2-phenyl-5-pyridin-4-yl-1H-pyrrole-3-carboxylic acid ethyl ester as a solid.

Workup

  1. customThe solvent was removed
  2. dissolutionthe residue was dissolved in 20 mL of EtOH
  3. waitthe reaction mixture was left overnight at rt
  4. concentrationThe reaction mixture was concentrated
  5. additionwater was added
  6. extractionthe slurry extracted with EtOAc
  7. washThe combined organic layers were washed with water
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude was purified by flash chromatography (DCM/MeOH 95:5)

Sources & evidence

ORD record
ord-1912ae73e3694ef8abf7db3f70f5e693
Source dataset
uspto-grants-2015_06
Patent number
US09056854B2

Reaction notes

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