Cesium carbonate → Ethyl 4-{4-[(dimethylamino)sulfonyl]-3-fluorophenoxy}-2-methyl-1-benzofuran-6-carboxylate

HRID 1177282Notes

Reaction equation

HRID 1177282 reaction equation
[OH:1][C:2]1[C:7]2[CH:8]=[C:9]([CH3:11])[O:10][C:6]=2[CH:5]=[C:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:3]=1.[F:17][C:18]1[CH:23]=[C:22](F)[CH:21]=[CH:20][C:19]=1[S:25]([N:28]([CH3:30])[CH3:29])(=[O:27])=[O:26].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.[Cu]I>[CH3:29][N:28]([CH3:30])[S:25]([C:19]1[CH:20]=[CH:21][C:22]([O:1][C:2]2[C:7]3[CH:8]=[C:9]([CH3:11])[O:10][C:6]=3[CH:5]=[C:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:3]=2)=[CH:23][C:18]=1[F:17])(=[O:27])=[O:26]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 11514065Ethyl 4-hydroxy-2-methylbenzofuran-6-carboxylateHCID 196843602,4-difluoro-N,N-dimethylbenzenesulfonamide

Product 1

HCID 59560433Ethyl 4-{4-[(dimethylamino)sulfonyl]-3-fluorophenoxy}-2-methyl-1-benzofuran-6-carboxylateYield 91%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 4-hydroxy-2-methyl-1-benzofuran-6-carboxylate (500 mg, 2.27 mmol), 2,4-difluoro-N,N-dimethylbenzenesulfonamide (553 mg, 2.75 mmol), Cs2CO3 (1.1 g, 4.12 mmol) and CuI (100 mg, 1 mmol) in DMF (20 mL) was heated to 100° C. for 4 hours. The solvent was removed under reduced pressure. The residue was poured into water (20 mL) and extracted with EtOAc (50 mL×2). The combined organic layers was washed with brine (20 mL×2), dried over Na2SO4 and concentrated. The product was purified via gradient silica gel column chromatography using EtOAc/Hex (10/90 to 30/70) to afford the desired compound (850 mg, 91%) as a white solid. 1 H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.41 (t, J=7.16 Hz, 3 H) 2.48 (s, 3 H) 2.78-2.94 (m, 6 H) 4.40 (q, J=7.10 Hz, 2 H) 6.24 (s, 1 H) 6.66-6.94 (m, 2 H) 7.65 (s, 1 H) 7.79 (t, J=8.38 Hz, 1 H) 8.04 (s, 1 H); MS (ESI, pos): 422.

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionThe residue was poured into water (20 mL)
  3. extractionextracted with EtOAc (50 mL×2)
  4. washThe combined organic layers was washed with brine (20 mL×2)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe product was purified via gradient silica gel column chromatography

Sources & evidence

ORD record
ord-dff8cebefd1243f78a6496492be282cb
Source dataset
uspto-grants-2010_11
Patent number
US07842713B2

Reaction notes

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