Cesium carbonate → 2-[6-(Thiazolo[4,5-b]pyridin-2-yloxy)-benzofuran-3-yl]-ethanol

HRID 1947479Notes

Reaction equation

HRID 1947479 reaction equation
[OH:1][CH2:2][CH2:3][C:4]1[C:8]2[CH:9]=[CH:10][C:11]([OH:13])=[CH:12][C:7]=2[O:6][CH:5]=1.C([O-])([O-])=O.[Cs+].[Cs+].Cl.Cl[C:22]1[S:23][C:24]2[C:25]([N:30]=1)=[N:26][CH:27]=[CH:28][CH:29]=2>CN(C=O)C>[S:23]1[C:24]2[C:25](=[N:26][CH:27]=[CH:28][CH:29]=2)[N:30]=[C:22]1[O:13][C:11]1[CH:10]=[CH:9][C:8]2[C:4]([CH2:3][CH2:2][OH:1])=[CH:5][O:6][C:7]=2[CH:12]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 574827652-Chlorothiazolo[4,5-b]pyridine hydrochlorideHCID 595777553-(2-Hydroxy-ethyl)-benzofuran-6-ol

Product 1

HCID 687706202-[6-(Thiazolo[4,5-b]pyridin-2-yloxy)-benzofuran-3-yl]-ethanolYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(2-hydroxy-ethyl)-benzofuran-6-ol (0.42 g, 2.4 mmol) in DMF (24 mL) was added Cs2CO3 (0.77 g, 2.4 mmol) and 2-chloro-thiazolo[4,5-b]pyridine hydrochloride (0.49 g, 2.4 mmol) and the reaction mixture was stirred (rt, 15 h) and then heated (50° C., 2 h). The reaction mixture was cooled (rt) and partitioned with EtOAc and brine (50 mL each). The aqueous layer was extracted with EtOAc (50 mL). The organic layer was washed with brine (50 mL), dried, filtered and concentrated in vacuo. The resulting residue was purified by silica gel flash chromatography using EtOAc:hexane (0-100%) to provide the title compound as an amber oil (0.42 g, 57%). MS (ESI): mass calcd. for C16H12N2O3S, 312.3; m/z not found. 1H NMR (500 MHz, CDCl3): 8.56 (dd, J=4.8, 1.7, 1H), 8.02 (dd, J=8.0, 1.6, 1H), 7.61-7.57 (m, 3H), 7.30 (dd, J=8.4, 2.2, 1H), 7.21 (dd, J=8.0, 4.8, 1H), 3.95 (q, J=6.1, 2H), 2.97-2.94 (m, 2H), 1.75 (t, J=5.5, 1H).

Workup

  1. temperatureheated (50° C., 2 h)
  2. temperatureThe reaction mixture was cooled (rt)
  3. custompartitioned with EtOAc and brine (50 mL each)
  4. extractionThe aqueous layer was extracted with EtOAc (50 mL)
  5. washThe organic layer was washed with brine (50 mL)
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-8b310d91a762492eb97637f482bdddf1
Source dataset
uspto-grants-2013_03
Patent number
US08399465B2

Reaction notes

Loading…