Triethylamine → 5-phenyl-1H-pyrrole-2-carboxylic acid methoxymethylamide

HRID 381499Notes

Reaction equation

HRID 381499 reaction equation
[C:1]1([C:7]2[NH:11][C:10]([C:12]([OH:14])=O)=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.CN[O:18][CH3:19].Cl.C(N=C=NCCC[N:29]([CH3:31])C)C.O.OC1C2N=NNC=2C=CC=1.CCN(CC)CC>>[CH3:19][O:18][CH2:31][NH:29][C:12]([C:10]1[NH:11][C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:8][CH:9]=1)=[O:14]

Participants

6

Reactant 5

HCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 2261995-phenyl-1H-pyrrole-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178526939HCID 178526939, compound

Product 1

HCID 544094405-phenyl-1H-pyrrole-2-carboxylic acid methoxymethylamide

Procedure

To a 200 mL round bottomed flask with a stirring bar and an argon inlet was added 5-phenyl-1H-pyrrole-2-carboxylic acid AV-5-1 (2.45 g, 13.09 mmol), N,O-dimethylhydroxylamine hydrochloride (1.40 g, 14.40 mmol), N-ethyl-N′-dimethylaminopropylcarbodiimide hydrochloride (2.76 g, 14.40 mmol), hydroxybenztriazole hydrate (1.94 g, 14.40 mmol) and dry, degassed DMF (25 mL). This well stirred mixture was warmed gently until all of the solids dissolved. Et3N (5.6 mL, 40.00 mmol) was added in one portion. The resulting mixture was stirred at ambient temperature 18 h. The solvents were removed in vacuo at +80° C. The residue was partitioned between saturated aqueous NaHCO3 and EtOAc. The layers were separated and the organic phase was washed with H2O (2×) and brine. Drying (MgSO4), filtration and removal of the solvent in vacuo gave a solid. This material was chromatographed on silica gel using 35% EtOAc in hexane as eluant to give 5-phenyl-1H-pyrrole-2-carboxylic acid methoxymethylamide AV-6-1 as a solid. 1H NMR (CDCl3) δ 3.36 (3H, s), 3.80 (3H, s), 6.58 (1H, dd, j=2.2, 4.0 Hz), 6.94 (1H, dd, j=2.2, 4.0 Hz), 7.30 (1H, m), 7.41 (2H, m), 7.58 (2H, m), 9.63 (1H, br s).

Workup

  1. customdry
  2. customdegassed DMF (25 mL)
  3. temperaturewas warmed gently until all of the solids
  4. dissolutiondissolved
  5. stirringThe resulting mixture was stirred at ambient temperature 18 h
  6. customThe solvents were removed in vacuo at +80° C
  7. customThe residue was partitioned between saturated aqueous NaHCO3 and EtOAc
  8. customThe layers were separated
  9. washthe organic phase was washed with H2O (2×) and brine
  10. customDrying
  11. filtration(MgSO4), filtration and removal of the solvent in vacuo
  12. customgave a solid
  13. customThis material was chromatographed on silica gel using 35% EtOAc in hexane as eluant

Sources & evidence

ORD record
ord-c1f6ac9b5c0743048bb2b31d4f7905a8
Source dataset
uspto-grants-2001_10
Patent number
US06306891B1

Reaction notes

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