Tetrahydrofuran → 1-(4-fluorobenzyl)-5-phenyl-1H-pyrrole-2-carboxylic acid methoxy-methylamide

HRID 381500Notes

Reaction equation

HRID 381500 reaction equation
CO[CH2:3][NH:4][C:5]([C:7]1[NH:8][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:10][CH:11]=1)=[O:6].C1C[O:21][CH2:20]C1.[H-].[Na+].[F:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Br)=[CH:28][CH:27]=1>CCOC(C)=O>[CH3:20][O:21][N:4]([CH3:3])[C:5]([C:7]1[N:8]([CH2:30][C:29]2[CH:32]=[CH:33][C:26]([F:25])=[CH:27][CH:28]=2)[C:9]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[CH:10][CH:11]=1)=[O:6]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 544094405-phenyl-1H-pyrrole-2-carboxylic acid methoxymethylamide

Product 1

HCID 206968041-(4-fluorobenzyl)-5-phenyl-1H-pyrrole-2-carboxylic acid methoxy-methylamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a 100 mL round bottomed flask containing 5-phenyl-1H-pyrrole-2-carboxylic acid methoxymethylamide AV-6-1 (0.692 g, 3.01 mmol) was added a stirring bar and an argon inlet was attached. THF (15 mL) was added and, when all of the solids had dissolved, NaH-oil suspension (0.132 g of a 60% w/w suspension, 3.31 mmol) was added. This mixture was stirred 15 min at ambient temperature then 4-fluorobenzylbromide (0.41 mL, 3.31 mmol) was added. The resulting mixture was stirred 24 h at ambient temperature. The mixture was diluted with EtOAc and the solution was washed with 1N HCl, water and brine. Drying (MgSO4), filtration and removal of the solvent in vacuo gave an oil. This material was chromatographed on silica gel using 25% EtOAc in hexanes a eluant to give 1-(4-fluorobenzyl)-5-phenyl-1H-pyrrole-2-carboxylic acid methoxy-methyl-amide AV-7-1. 1H NMR (CDCl3) δ 3.21 (3H, s), 3.47 (3H, s), 5.52 (2H, s), 6.24 (1H, d, j=3.9 Hz), 6.75 to 6.90 (5H, m), 6.94 (1H, d, j=3.9 Hz), 7.38 (4H, m).

Workup

  1. additionwas added a stirring bar and an argon inlet
  2. dissolutionwhen all of the solids had dissolved
  3. stirringThe resulting mixture was stirred 24 h at ambient temperature
  4. washthe solution was washed with 1N HCl, water and brine
  5. customDrying
  6. filtration(MgSO4), filtration and removal of the solvent in vacuo
  7. customgave an oil
  8. customThis material was chromatographed on silica gel using 25% EtOAc in hexanes a eluant

Sources & evidence

ORD record
ord-7b8418e229524a65954b599ae113f6d1
Source dataset
uspto-grants-2001_10
Patent number
US06306891B1

Reaction notes

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