Cesium carbonate → tert-Butyl 4-(5-chloro-6-methylpyridin-3-yl)-3-methylbenzoate

HRID 531249Notes

Reaction equation

HRID 531249 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:21]=[CH:20][C:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:11][C:10]=2[CH3:22])[CH:5]=[N:6][C:7]=1Cl.[CH3:23][B-](F)(F)F.[K+].C([O-])([O-])=O.[Cs+].[Cs+].O1CCOCC1>O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:21]=[CH:20][C:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:11][C:10]=2[CH3:22])[CH:5]=[N:6][C:7]=1[CH3:23]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 23692566Potassium Trifluoro(methyl)borateHCID 90009177tert-Butyl 4-(5,6-dichloropyridin-3-yl)-3-methylbenzoate

Product 1

HCID 118021442tert-Butyl 4-(5-chloro-6-methylpyridin-3-yl)-3-methylbenzoate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of tert-butyl 4-(5,6-dichloropyridin-3-yl)-3-methylbenzoate (Step A, 650 mg, 1.92 mmol), potassium methyltrifluoroborate (234 mg, 1.92 mmol), Cs2CO3 (1.88 g, 5.77 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (157 mg, 0.192 mmol), dioxane (4 mL) and water (0.25 mL) was flushed with nitrogen and stirred at 110° C. for 2 hours. After cooling down, the mixture was filtered over celite. The filter cake was washed with ethyl acetate and further diluted with ethyl acetate and water. After separating the layers, the organic was washed with brine. The organic layer was dried over sodium sulfate, filtered and the filtrate was concentrated. The crude isolate was purified by silica gel chromatography (0 to 80% ethyl acetate/hexane) to give the titled compound as a white solid. 1H NMR (500 MHz, CDCl3): δ 8.38 (d, J=1.9 Hz, 1H), 7.94 (s, 1H), 7.90 (d, J=8.0 Hz, 1H), 7.63 (d, J=1.8 Hz, 1H), 7.27 (d, J=7.9 Hz, 1H), 2.7 (s, 3H), 2.35 (s, 3H), 1.64 (s, 9H).

Workup

  1. customwas flushed with nitrogen
  2. temperatureAfter cooling down
  3. filtrationthe mixture was filtered over celite
  4. washThe filter cake was washed with ethyl acetate
  5. additionfurther diluted with ethyl acetate and water
  6. customAfter separating the layers
  7. washthe organic was washed with brine
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated
  11. customThe crude isolate
  12. customwas purified by silica gel chromatography (0 to 80% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9e2b39dd922a4f29bb8cde2f93d287ec
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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