Cesium carbonate → Tert-butyl (4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)carbamate

HRID 626539Notes

Reaction equation

HRID 626539 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[C:18](=[O:25])([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[NH2:19].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].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]>[N+:15]([C:12]1[N:11]=[CH:10][C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:19][C:18](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH:7]=2)=[CH:14][CH:13]=1)([O-:17])=[O:16]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 593227792-Chloro-4-((6-nitropyridin-3-yl)oxy)pyridine

Product 1

HCID 131735222Tert-butyl (4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)carbamateYield 76%

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of Example A1 (1.5 g, 5.96 mmol) in dioxane (50 mL) was sparged with Ar, treated with tert-butyl carbamate (1.536 g, 13.11 mmol), Cs2CO3 (3.88 g, 11.92 mmol) and DPPF (0.420 g, 0.775 mmol), sparged with Ar, treated with Pd2(dba)3 (0.382 g, 0.417 mmol), sparged again with Ar and heated at 100° C. overnight. The mixture was cooled to RT, diluted with EtOAc, the solids removed via filtration through diatomaceous earth and washed with EtOAc. The filtrate was concentrated to dryness, treated with MeCN, sonicated and the solid collected via filtration. The filtrate was concentrated to dryness, treated again with MeCN and the solid collected. The filtrate was again concentrated to dryness, purified via silica gel chromatography (EtOAc/Hex) and combined with the two above-isolated solids to afford tert-butyl (4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)carbamate (1.5 g, 76%). MS (ESI) m/z: 333.1 (M+H+).

Workup

  1. customsparged with Ar
  2. customsparged again with Ar
  3. temperatureThe mixture was cooled to RT
  4. additiondiluted with EtOAc
  5. customthe solids removed via filtration through diatomaceous earth
  6. washwashed with EtOAc
  7. concentrationThe filtrate was concentrated to dryness
  8. additiontreated with MeCN
  9. customsonicated
  10. filtrationthe solid collected via filtration
  11. concentrationThe filtrate was concentrated to dryness
  12. additiontreated again with MeCN
  13. customthe solid collected
  14. concentrationThe filtrate was again concentrated to dryness
  15. custompurified via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record
ord-2a92993fe3934666981fbe27fb5e1b2b
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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