Cesium carbonate → 5-Methoxy-7-methylbenzofuran

HRID 920122Notes

Reaction equation

HRID 920122 reaction equation
Br[C:2]1[C:10]2[O:9][CH:8]=[CH:7][C:6]=2[CH:5]=[C:4]([O:11][CH3:12])[CH:3]=1.[CH3:13]B(O)O.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:12][O:11][C:4]1[CH:3]=[C:2]([CH3:13])[C:10]2[O:9][CH:8]=[CH:7][C:6]=2[CH:5]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 139377Methylboronic AcidHCID 221447037-Bromo-5-methoxy-1-benzofuran

Product 1

HCID 680164105-Methoxy-7-methylbenzofuranYield 38.5%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of the product from Step C (3.6 g, 16 mmol), methylboronic acid (1.4 g, 24 mmol), Pd(dppf)2Cl2 (0.65 g, 0.8 mmol) and Cs2CO3 (13.0 g, 40 mmol) in 1,4-dioxane (50 mL) and H2O (10 mL) was refluxed for 3 hrs under N2 atmosphere. The reaction was cooled to room temperature and filtered through a celite pad. The filtrate was diluted with EtOAc (200 mL) and washed with brine (50 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica column chromatography (eluted with PE) to afford the title compound (1.0 g, 38%) as an oil. 1H-NMR (600 MHz, CDCl3) δ 7.63 (d, J=1.6 Hz, 1H), 6.92 (d, J=2.1 Hz, 1H), 6.76 (s, 1H), 6.73 (d, J=1.8 Hz, 1H), 3.86 (s, 3H), 2.53 (s, 3H) ppm.

Workup

  1. temperaturewas refluxed for 3 hrs under N2 atmosphere
  2. filtrationfiltered through a celite pad
  3. additionThe filtrate was diluted with EtOAc (200 mL)
  4. washwashed with brine (50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica column chromatography (eluted with PE)

Sources & evidence

ORD record
ord-e39049a87c1c4c048063be2420d14a38
Source dataset
uspto-grants-2016_03
Patent number
US09273046B2

Reaction notes

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