Potassium Phosphate, Tribasic → Ethyl 3-(2-aminopyridin-4-yloxy)-4-chlorobenzoate

HRID 911034Notes

Reaction equation

HRID 911034 reaction equation
[Cl:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][C:3]=1[O:13][C:14]1[CH:19]=[CH:18][N:17]=[C:16](Cl)[CH:15]=1.C(=O)(OC(C)(C)C)[NH2:22].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C.C1(C)C=CC=CC=1>[NH2:22][C:16]1[CH:15]=[C:14]([O:13][C:3]2[CH:4]=[C:5]([CH:11]=[CH:12][C:2]=2[Cl:1])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH:19]=[CH:18][N:17]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86634737Ethyl 4-chloro-3-(2-chloropyridin-4-yloxy)benzoate

Product 1

HCID 66617829Ethyl 3-(2-aminopyridin-4-yloxy)-4-chlorobenzoateYield 37.51%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A flask was charged with ethyl 4-chloro-3-(2-chloropyridin-4-yloxy)benzoate (16.347 g, 52.369 mmol), tert-butyl carbamate (18.405 g, 157.11 mmol), potassium phosphate (12.228 g, 57.606 mmol), and toluene (150 mL). The flask was degassed with nitrogen, and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (3.0302 g, 5.2369 mmol) and tris(dibenzylideneacetone)dipalladium (0) (2.3978 g, 2.6185 mmol) were added. The flask was degassed again, and degassed water (40 mL) was added. The reaction was heated at 90° C. overnight. Water was added and the reaction mixture was extracted with ethyl acetate and concentrated. TFA (100 mL) was added and the mixture was stirred overnight, then concentrated, treated with sodium bicarbonate, and extracted with ethyl acetate. The organic layer was dried and concentrated. The residue was purified by silica gel column chromatography eluting with 20-25% ethyl acetate in hexanes and then ethyl acetate to provide the desired product (5.75 g, 37.510% yield) as yellow oily semi solid.

Workup

  1. additionwere added
  2. customThe flask was degassed again
  3. customdegassed water (40 mL)
  4. additionwas added
  5. additionWater was added
  6. extractionthe reaction mixture was extracted with ethyl acetate
  7. concentrationconcentrated
  8. additionTFA (100 mL) was added
  9. concentrationconcentrated
  10. additiontreated with sodium bicarbonate
  11. extractionextracted with ethyl acetate
  12. customThe organic layer was dried
  13. concentrationconcentrated
  14. customThe residue was purified by silica gel column chromatography
  15. washeluting with 20-25% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-7fe5bbf9b15344a884b7ea2985bf6516
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

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