Potassium Phosphate, Tribasic → HCID 66617836, compound

HRID 911093Notes

Reaction equation

HRID 911093 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]([CH3:21])=[N:11][CH:12]=[C:13]([C:19]=2[CH3:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:5]=[CH:4][N:3]=1.C(=O)(OC(C)(C)C)[NH2:23].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>C1(C)C=CC=CC=1.O.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]>[NH2:23][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]([CH3:21])=[N:11][CH:12]=[C:13]([C:19]=2[CH3:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:5]=[CH:4][N:3]=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 86634793HCID 86634793, compound

Product 1

HCID 66617836HCID 66617836, compoundYield 54%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A round bottom flask containing ethyl 5-(2-chloropyridin-4-yloxy)-4,6-dimethylnicotinate (7.5 g, 25 mmol), tert-butyl carbamate (8.6 g, 73 mmol), potassium phosphate (tribasic) (5.7 g, 27 mmol), tris(dibenzylideneacetone)dipalladium (1.1 g, 1.2 mmol), and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (1.1 g, 1.8 mmol) was suspended in toluene (200 mL) and water (40 mL). The solution was degassed with nitrogen and then stirred at 90 C for 4 hours. The solution was filtered through GF/F paper and diluted with water. The material was then extracted with EtOAc and the organic layer was dried, and concentrated. The residue was then slowly diluted in TFA (50 mL) and stirred at room temperature for 6 hours. The solution was concentrated, diluted with water, and neutralized with saturated NaHCO3 solution. The material was extracted with EtOAc and the organic layer was dried, and concentrated. Flash chromatography (10% MeOH/EtOAc) gave ethyl 5-(2-aminopyridin-4-yloxy)-4,6-dimethylnicotinate (3.8 g, 54%).

Workup

  1. customThe solution was degassed with nitrogen
  2. filtrationThe solution was filtered through GF/F paper
  3. additiondiluted with water
  4. extractionThe material was then extracted with EtOAc
  5. customthe organic layer was dried
  6. concentrationconcentrated
  7. additionThe residue was then slowly diluted in TFA (50 mL)
  8. stirringstirred at room temperature for 6 hours
  9. concentrationThe solution was concentrated
  10. additiondiluted with water
  11. extractionThe material was extracted with EtOAc
  12. customthe organic layer was dried
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-519f6e5a62c04ecd97bc510d690d5d83
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

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