Tetrahydrofuran → 1-[1-(4-fluorobenzyl)-5-phenyl-1H-pyrrol-2-yl]ethanone

HRID 381501Notes

Reaction equation

HRID 381501 reaction equation
CON(C)[C:4]([C:6]1[N:7]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:9][CH:10]=1)=[O:5].[CH2:26]1COCC1.C[Li]>CCOCC>[F:24][C:21]1[CH:20]=[CH:19][C:18]([CH2:17][N:7]2[C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[CH:9][CH:10]=[C:6]2[C:4](=[O:5])[CH3:26])=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 206968041-(4-fluorobenzyl)-5-phenyl-1H-pyrrole-2-carboxylic acid methoxy-methylamideHCID 178418348HCID 178418348, compound

Product 1

HCID 183634681-[1-(4-fluorobenzyl)-5-phenyl-1H-pyrrol-2-yl]ethanone

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

To a 100 mL round bottomed flask with a stirring bar and an argon inlet was added 1-(4-fluorobenzyl)-5-phenyl-1H-pyrrole-2-carboxylic acid methoxy-methylamide AV-7-1 (0.726 g, 2.16 mmol) and dry THF (20 mL). This solution was cooled to −78° C. and methyllithium (3.39 mL of a 1.4 M solution in Et2O, 4.75 mmol). The mixture was stirred 30 min at −78° C. then the reaction was quenched with saturated aqueous NH4Cl solution. The mixture was warmed to room temperature and stirred 2 h. The layers were separated and the aqueous phase was extracted with EtOAc. The combined organic fractions were dried (MgSO4), filtered and concentrated in vacuo. The crude product was chromatographed on silica gel using 15% EtOAc in hexanes as eluant to give 1-[1-(4-fluorobenzyl)-5-phenyl-1H-pyrrol-2-yl]ethanone AV-8-1 as an oil. 1H NMR (CDCl3) δ 2.42 (3H, s), 5.59 (2H, s), 6.29 (1H, d, j=4.2 Hz), 6.78 to 6.91 (4H, m), 7.12 (1H, d, j=4.2 Hz), 7.29 (2H, m), 7.38 (3H, m).

Workup

  1. customthe reaction was quenched with saturated aqueous NH4Cl solution
  2. temperatureThe mixture was warmed to room temperature
  3. stirringstirred 2 h
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with EtOAc
  6. dry with materialThe combined organic fractions were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was chromatographed on silica gel using 15% EtOAc in hexanes as eluant

Sources & evidence

ORD record
ord-5d8f5ee6a2f745689659f1f30b10d3e2
Source dataset
uspto-grants-2001_10
Patent number
US06306891B1

Reaction notes

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