Potassium Carbonate → 2-(5-(Tert-butyl)-2-methoxyphenyl)-5-methylpyridine

HRID 1480613Notes

Reaction equation

HRID 1480613 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.[C:9]([C:13]1[CH:14]=[CH:15][C:16]([O:22][CH3:23])=[C:17](B(O)O)[CH:18]=1)([CH3:12])([CH3:11])[CH3:10].C(=O)([O-])[O-].[K+].[K+]>C(COC)OC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:9]([C:13]1[CH:18]=[CH:17][C:16]([O:22][CH3:23])=[C:15]([C:2]2[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=2)[CH:14]=1)([CH3:12])([CH3:10])[CH3:11]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 5642162-Bromo-5-methylpyridineHCID 147405795-(tert-Butyl)-2-methoxybenzeneboronic acid2×

Product 1

HCID 867185702-(5-(Tert-butyl)-2-methoxyphenyl)-5-methylpyridineYield 99%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-bromo-5-methylpyridine [purchased from TCI] (0.827 g, 4.81 mmol), (5-(tert-butyl)-2-methoxyphenyl)boronic acid [Intermediate 5] (1.2 g, 5.77 mmol) and potassium carbonate (0.997 g, 7.21 mmol) in dimethoxyethane (15 mL) and water (5 mL) was purged with nitrogen for 20 minutes. Tetrakis(triphenylphosphine)palladium(0) (277.8 mg, 0.24 mmol) was added and the reaction mixture heated to 80° C. in a sealed vial for 22 hours. The cooled reaction mixture was partitioned between ethyl acetate (80 mL) and 1 M aqueous sodium hydroxide solution (80 mL), the organic phase separated, washed with water (80 mL) and saturated brine (80 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give a yellow syrup. The crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 35% ethyl acetate in hexanes to give 2-(5-(tert-butyl)-2-methoxyphenyl)-5-methylpyridine (1.216 g, 99% yield) as a colorless oil.

Workup

  1. customwas purged with nitrogen for 20 minutes
  2. customThe cooled reaction mixture
  3. customwas partitioned between ethyl acetate (80 mL) and 1 M aqueous sodium hydroxide solution (80 mL)
  4. customthe organic phase separated
  5. washwashed with water (80 mL) and saturated brine (80 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give a yellow syrup
  10. customThe crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 35% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-aac6ee9d5ff94983858b1920425c3d21
Source dataset
uspto-grants-2016_08
Patent number
US09409893B2

Reaction notes

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