Benzofuran-2-carboxylic acid → HCID 67109825, compound

HRID 29453

Reaction equation

HRID 29453 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:11].[C:13]([O:17][C:18](=[O:40])[CH:19]([NH:23][S:24]([C:27]1[CH:32]=[CH:31][C:30]([C:33]2[CH:38]=[CH:37][C:36](O)=[CH:35][CH:34]=2)=[CH:29][CH:28]=1)(=[O:26])=[O:25])[CH:20]([CH3:22])[CH3:21])([CH3:16])([CH3:15])[CH3:14]>ClCCl.CN(C)C1C=CN=CC=1>[C:13]([O:17][C:18]([CH:19]([NH:23][S:24]([C:27]1[CH:28]=[CH:29][C:30]([C:33]2[CH:38]=[CH:37][C:36]([O:11][C:10]([C:2]3[O:1][C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=4[CH:3]=3)=[O:12])=[CH:35][CH:34]=2)=[CH:31][CH:32]=1)(=[O:25])=[O:26])[CH:20]([CH3:22])[CH3:21])=[O:40])([CH3:15])([CH3:16])[CH3:14]

Participants

5

Reactant 2

HCID 10331Benzofuran-2-carboxylic acidHCID 671099642-(4'-Hydroxy-biphenyl-4-sulfonylamino)-3-methyl-butyric acid tert-butyl ester

Product 1

HCID 67109825HCID 67109825, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To benzofuran-2-carboxylic acid (0.401 g, 2.47 mmol, 1 equiv.) dissolved in dry dichloromethane (50 mL) was added dicyclohexylcarbidiimide (1.019 g, 4.94 mmol, 2 equiv) and the mixture was stirred under nitrogen for 15 minutes. Then 2-(4′-hydroxy-biphenyl-4-sulfonylamino)-3-methyl-butyric acid tert-butyl ester (1.0 g, 2.47 mmol, 1 equiv., Example 134, Step 1) was introduced to the reaction mixture, followed by the addition of 4-dimethylamino pyridine (0.050 g, 0.41 mmol). The mixture was allowed to stir at room temperature overnight. The reaction mixture was then diluted with dichloromethane, washed with water and brine. The organic layer was dried over magnesium sulfate and the solvent was concentrated in vacuo. The residue was dissolved in ethyl acetate and purified by column chromatography on silica gel eluting with 20% ethyl acetate/hexane to afford 325 mg of benzofuran-2-carboxylic acid 4′-(1-tert-butoxycarbonyl-2-methyl-propylsulfamoyl)-biphenyl-4-yl ester in 31% yield. 1H NMR (400 MHz, CDCl3) δ ppm 0.87 (d, J=6.82 Hz, 3 H) 1.03 (d, J=6.82 Hz, 3 H) 1.21 (s, 9 H) 2.07 (m, 1 H) 3.68 (dd, J=9.85, 4.55 Hz, 1 H) 5.15 (d, J=9.85 Hz, 1 H) 7.37 (m, 3 H) 7.53 (t, J=7.83 Hz, 1 H) 7.66 (m, 5 H) 7.77 (m, 2 H) 7.92 (d, J=8.34 Hz, 2 H).

Workup

  1. additionwas added dicyclohexylcarbidiimide (1.019 g, 4.94 mmol, 2 equiv)
  2. stirringto stir at room temperature overnight
  3. washwashed with water and brine
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. concentrationthe solvent was concentrated in vacuo
  6. dissolutionThe residue was dissolved in ethyl acetate
  7. custompurified by column chromatography on silica gel eluting with 20% ethyl acetate/hexane

Sources & evidence

ORD record
ord-12c3ac35267f4083a7b2601d61d8b6da
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Linked notes

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