Benzofuran-2-carboxylic acid → 2-Benzofurancarboxamide, N-(4-hydroxybutyl)-

HRID 2417210Notes

Reaction equation

HRID 2417210 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]([OH:12])=O.[NH2:13][CH2:14][CH2:15][CH2:16][CH2:17][OH:18].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>CN(C=O)C>[OH:18][CH2:17][CH2:16][CH2:15][CH2:14][NH:13][C:10]([C:2]1[O:1][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=1)=[O:12]

Participants

7

Reactant 5

HCID 10331Benzofuran-2-carboxylic acidHCID 258684-Amino-1-butanolHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 109554572-Benzofurancarboxamide, N-(4-hydroxybutyl)-Yield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Benzofurancarboxylic acid (5.0 g, 30.8 mmol) and 4-amino-1-butanol (3.4 ml, 37 mmol) were dissolved in DMF (45 ml). 1-hydroxybenzotriazole (5.0 g, 37 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (7.7 g, 40 mmol), and diisopropylethylamine (10.7 ml, 61.7 mmol) were added sequentially to the solution and allowed to stir at room temperature overnight. After removing excess solvent in vacuo, the residue was taken up in water and the product was extracted into dichloromethane. The organics were combined, washed with brine, dried over Na2SO4, and solvent removed in vacuo to give a solid which was purified by column chromatography (100% ethyl acetate) to give 3.5 g (50% yield) of a white solid. 1H NMR (DMSO-d6): δ 1.35-1.62 (m, CH2, CH2), 3.29 (q, CH2), 3.41 (q, CH2), 4.3 (t, NH), 7.78 (d, 1 Ar H), 7.63 (d, 1 Ar H), 7.51 (s, 1 Ar H), 7.46 (t, 1 Ar H), 7.35 (t, 1 Ar H), 8.71 (t, NH) Electrospray Mass Spec: m/z 234.2 (M+H)+.

Workup

  1. customAfter removing excess solvent in vacuo
  2. extractionthe product was extracted into dichloromethane
  3. washwashed with brine
  4. dry with materialdried over Na2SO4, and solvent
  5. customremoved in vacuo
  6. customto give a solid which
  7. customwas purified by column chromatography (100% ethyl acetate)

Sources & evidence

ORD record
ord-4ac88bfe08494e669ea7a5dc044952c0
Source dataset
uspto-grants-2004_11
Patent number
US06825352B2

Reaction notes

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