Potassium Carbonate → Methyl 4-(6-methoxypyridin-3-yl)-3,5-dimethylbenzoate

HRID 531246Notes

Reaction equation

HRID 531246 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH3:21])[C:11]=1B1OC(C)(C)C(C)(C)O1)[C:5]([O:7][CH3:8])=[O:6].Br[C:23]1[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[N:27][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].O1CCOCC1>[CH3:30][O:29][C:26]1[N:27]=[CH:28][C:23]([C:11]2[C:10]([CH3:21])=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=2[CH3:1])=[CH:24][CH:25]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27348955-Bromo-2-methoxypyridineHCID 68021937Methyl 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate

Product 1

HCID 90009124Methyl 4-(6-methoxypyridin-3-yl)-3,5-dimethylbenzoate

Reagents, catalysts & solvents 2

HCID 178454861HCID 178454861, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Methyl 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (Step A, 2.79 g, 7.20 mmol), 1,1′-bis(di-tert-butylphoshino)ferrocene palladium dichloride (0.391 g, 0.600 mmol) and 5-bromo-2-methoxypyridine (0.776 mL, 6 mmol) were mixed in a reaction flask which was then evacuated and charged with nitrogen three times. Added 1,4-dioxane (30.0 mL) and 3.0M aqueous potassium carbonate (6.00 mL, 18.00 mmol), evacuated and charged with nitrogen (3×), then stirred overnight at 80° C. The reaction was then partitioned between ethyl acetate and water. After a second water wash, the organic was dried over sodium sulfate, filtered and evaporated. The crude was purified by silica gel chromatography, eluting with 10 column volumes of 4% ethyl acetate/hexanes followed by a gradient of 4-10% ethyl acetate/hexanes over 10 column volumes to give the title compound. 1H NMR (CDCl3, 500 MHz) δ7.94 (d, 1H), 67.79 (s, 2H), 67.36 (dd, 1H), 66.84 (d, 1H), 64.00 (s, 3H), 63.93 (s, 3H), 62.09 (s, 6H).

Workup

  1. customwas then evacuated
  2. additioncharged with nitrogen three times
  3. additioncharged with nitrogen (3×)
  4. customThe reaction was then partitioned between ethyl acetate and water
  5. washAfter a second water wash
  6. dry with materialthe organic was dried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude was purified by silica gel chromatography
  10. washeluting with 10 column volumes of 4% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-6a33b7209045487d9cb1d3b95263d935
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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