Cesium carbonate → tert-Butyl 4-formyl-6-methoxypyridin-2-ylcarbamate

HRID 1355535Notes

Reaction equation

HRID 1355535 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][CH3:11])[N:9]=1)[CH:5]=[O:6].C([O-])([O-])=O.[Cs+].[Cs+].[CH3:18][C:19]1(C)[C:45]2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=C[C:20]1=2.C([NH:64][C:65](=[O:67])[O-:66])(C)(C)C>O1CCOCC1.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]>[CH:5]([C:4]1[CH:7]=[C:8]([O:10][CH3:11])[N:9]=[C:2]([NH:64][C:65](=[O:67])[O:66][C:19]([CH3:45])([CH3:20])[CH3:18])[CH:3]=1)=[O:6]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27629762-Chloro-6-methoxypyridine-4-carbaldehydeHCID 21252905Tert-butylcarbamate

Product 1

HCID 18506791tert-Butyl 4-formyl-6-methoxypyridin-2-ylcarbamate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-chloro-6-methoxyisonicotinaldehyde (15-2, 500 mg, 2.91 mmole) in dry dioxane (5 mL) was added Cs2CO3 (1.42 g, 4.37 mmole), Xanthphos (253 mg, 0.44 mmole), Pd2(dba)3 (133 mg, 0.15 mmole), and tert-butylcarbamate (410 mg, 3.5 mmole) then the mixture was heated to reflux. After 18 hr the mixture was cooled to RT., diluted with H2O, and extracted with EtOAc (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated. Flash column chromatography (gradient, 0-10% EtOAc/hexanes) gave the titled compound as an orange solid. 1H-NMR (500 MHz, CDCl3) δ 9.98 (s, 1 H), 7.91 (s, 1 H), 6.82 (s, 1 H), 3.88 (s, 3 H), 1.54 (s, 9 H); MS (ES) (M+H)+ 253.

Workup

  1. temperaturethe mixture was heated to reflux
  2. extractionextracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-1aa8300bf7c1460886c75587557949f7
Source dataset
uspto-grants-2003_07
Patent number
US06586424B2

Reaction notes

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