Ethyl Acetate → Methyl 7-(4-amino-3-fluorophenoxy)thieno[3,2-b]pyridine-2-carboxylate

HRID 2407214Notes

Reaction equation

HRID 2407214 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[S:10][C:3]=12.[NH2:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][C:17]=1[F:23].C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>CS(C)=O.ClCCl.[Cu]Cl.O>[NH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:2]2[CH:7]=[CH:6][N:5]=[C:4]3[CH:8]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[S:10][C:3]=23)=[CH:18][C:17]=1[F:23]

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 27359194-Amino-3-fluorophenolHCID 59424429Methyl 7-chlorothieno[3,2-B]pyridine-2-carboxylate

Product 1

HCID 67042609Methyl 7-(4-amino-3-fluorophenoxy)thieno[3,2-b]pyridine-2-carboxylate

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Methyl 7-chlorothieno[3,2-b]pyridine-2-carboxylate (5 g, 0.022 mol) and the 4-amino-3-fluorophenol (3.3 g, 0.026 mol) were added to a round bottom flask containing cesium carbonate (14.8 g, 0.045 mol), ethyl-2-cyclohexanone carboxylate (0.73 g, 0.004 mol), and copper (I) chloride (0.22 g, 0.002 mol). The mixture was diluted with DMSO (250 mL) and stirred at 70 C under an atmosphere of nitrogen for 2 hours. The dark reaction mixture was cooled to room temperature and poured into ethyl acetate (500 mL)/water (1 L) with vigorous stirring. The mixture was filtered through celite and the organic portion of the filtrate was separated and dried over magnesium sulfate. The solution was filtered and the filtrate was concentrated to give a purple viscous liquid. The crude product was taken up in dichloromethane and passed through a silica gel column eluting with 1:1 hexane/ethyl acetate. Fractions containing the product were combined and concentrated to afford methyl 7-(4-amino-3-fluorophenoxy)thieno[3,2-b]pyridine-2-carboxylate as red solid. Yield: 1.62 g (23%); MS [M+H]+ 319.1

Workup

  1. customThe dark reaction mixture
  2. filtrationThe mixture was filtered through celite
  3. customthe organic portion of the filtrate was separated
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe solution was filtered
  6. concentrationthe filtrate was concentrated
  7. customto give a purple viscous liquid
  8. washeluting with 1:1 hexane/ethyl acetate
  9. additionFractions containing the product
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-a27b170409364ad4888fecbbbd44e195
Source dataset
uspto-grants-2014_08
Patent number
US08809534B2

Reaction notes

Loading…