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

HRID 991742Notes

Reaction equation

HRID 991742 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): δ1.35-1.62 (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-283fcab01fbe47e1b3b313f5e69436c2
Source dataset
uspto-grants-2002_10
Patent number
US06465508B1

Reaction notes

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