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

HRID 911034Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 911034
[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

Komponenten

8

Edukt 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

Produkt 1

HCID 66617829Ethyl 3-(2-aminopyridin-4-yloxy)-4-chlorobenzoateAusbeute 37,51 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-7fe5bbf9b15344a884b7ea2985bf6516
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08022222B2

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