Sodium Carbonate → (5-Chlorobenzofuran-3-yl)methanol

HRID 2046093Notes

Reaction equation

HRID 2046093 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4](I)[CH:3]=1.C([Si]([O:17][CH2:18][C:19]#[C:20][Si](C(C)(C)C)(C)C)(C)C)(C)(C)C.[Li+].[Cl-].C([O-])([O-])=O.[Na+].[Na+].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CN(C=O)C.C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]2[O:8][CH:20]=[C:19]([CH2:18][OH:17])[C:4]=2[CH:3]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 6202344-Chloro-2-iodophenolHCID 2724141Tetrabutylammonium FluorideHCID 10968062HCID 10968062, compound

Product 1

HCID 3757833(5-Chlorobenzofuran-3-yl)methanolYield 99%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 4-chloro-2-iodophenol (1 g, 3.92 mmol), tert-butyl(3-(tert-butyldimethylsilyl)prop-2-ynyloxy)-dimethylsilane (1.93 g, 6.8 mmol), LiCl (0.15 g; 3.5 mmol) and Na2CO3 (0.636 g; 6 mmol) in anhydrous DMF (10 ml) Pd(OAc)2 (0.3 g) was added at 100° C. under N2 and heating was continued for 1.5 h. The solvent was removed in vacuo and the residue was diluted to 100 ml with EtOAc, washed with H2O, dried over MgSO4 and filtered. The filtrate was evaporated to dryness and the residue was purified by FCC (SiO2, hexane/EtOAc) to give the coupling product (0.64 g; 26%). This was dissolved in THF (5 ml) and 1M TBAF in THF (2 ml) was added to it and the mixture was stirred for 4 h at reflux. The solvent was distilled off and the residue was dilute to 50 ml with EtOAc, washed with 1M HCl, H2O, dried over MgSO4 and filtered. The filtrate was evaporated to dryness and the residue was purified by FCC (SiO2, hexane/EtOAc) to give the title compound (0.33 g; 99%), as creamy paste. 1H-NMR (CDCl3) 7.63 (d, 1H, J=2.11 Hz); 6.60 (b, 1H); 7.37 (d, 1H, J=8.72 Hz); 7.25 (dd, 1H, J=8.71, 2.13 Hz); 4.79 (s, 2H).

Workup

  1. additionwas added at 100° C. under N2
  2. temperatureheating
  3. customThe solvent was removed in vacuo
  4. additionthe residue was diluted to 100 ml with EtOAc
  5. washwashed with H2O
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customThe filtrate was evaporated to dryness
  9. customthe residue was purified by FCC (SiO2, hexane/EtOAc)
  10. customto give the coupling product (0.64 g; 26%)
  11. temperatureat reflux
  12. distillationThe solvent was distilled off
  13. additionthe residue was dilute to 50 ml with EtOAc
  14. washwashed with 1M HCl, H2O
  15. dry with materialdried over MgSO4
  16. filtrationfiltered
  17. customThe filtrate was evaporated to dryness
  18. customthe residue was purified by FCC (SiO2, hexane/EtOAc)

Sources & evidence

ORD record
ord-5cdabb8515f9444da4252a987d142967
Source dataset
uspto-grants-2013_11
Patent number
US08592399B2

Reaction notes

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