Cesium carbonate → Tert-butyl 4-formyl-6-methylpyridin-2-ylcarbamate

HRID 1814016Notes

Reaction equation

HRID 1814016 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH:8]=[O:9])[CH:5]=[C:4]([CH3:10])[N:3]=1.C([NH:15][C:16](=[O:18])[O-:17])(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:25][C:26]1(C)[C:52]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:27]1=2>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:8]([C:6]1[CH:5]=[C:4]([CH3:10])[N:3]=[C:2]([NH:15][C:16](=[O:18])[O:17][C:26]([CH3:52])([CH3:27])[CH3:25])[CH:7]=1)=[O:9]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27629752-Chloro-6-methylpyridine-4-carbaldehydeHCID 21252905Tert-butylcarbamate

Product 1

HCID 22504283Tert-butyl 4-formyl-6-methylpyridin-2-ylcarbamate

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

2-Chloro-6-methyl-pyridine-4-carbaldehyde (13-2, 0.609 g, 3.91 mmol), tert-butylcarbamate (0.550 g, 4.70 mmol), cesium carbonate (1.91 g, 5.87 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.036 g, 0.040 mmol) and Xantphos (0.068 g, 0.030 mmol) were stirred in 10 mL of anhydrous dioxane under N2. The reaction was heated to 80° C. and after 18 hours the reaction was cooled to room temperature. The mixture was diluted with water and extracted 3× with EtOAc. The extracts were dried over Na2SO4, filtered and concentrated. Purification by flash column chromatography afforded impure tert-butyl 4-formyl-6-methylpyridin-2-ylcarbamate. This aldehyde was dissolved in 2 mL of 1,2-dichloroethane. N-Acetylpiperazine (0.074 g, 0.58 mmol) was added followed by addition of 0.05 mL HOAc and NaBH(OAc)3 (0.122 g, 0.58 mmol). After 3 hours the reaction was quenched by the addition of half-saturated NaHCO3 (aq). The mixture was extracted 3× with DCM (dichloromethane) and the extracts were dried over Na2SO4, filtered and concentrated to afford the titled compound, 13-3. 1H NMR (CDCl3) δ 7.67 (s, 1H), 7.47 (s, 1H), 6.84 (s, 1H), 3.64 (t, 2H, J=4.9 Hz), 3.47 (m, 4H), 2.44 (m, 7H), 2.09 (s, 3H), 1.51 (s, 9H).

Workup

  1. temperaturewas cooled to room temperature
  2. extractionextracted 3× with EtOAc
  3. dry with materialThe extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-1826ff4524a340659fde683f16c80777
Source dataset
uspto-grants-2005_04
Patent number
US06875767B2

Reaction notes

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