Potassium Carbonate → 4-(Adamantan-1-ylmethoxy)-3-(2-methoxypyridin-3-yl)benzonitrile

HRID 1849499Notes

Reaction equation

HRID 1849499 reaction equation
[C:1]12([CH2:11][O:12][C:13]3[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][C:14]=3Br)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C(=O)([O-])[O-].[K+].[K+].[CH3:28][O:29][C:30]1[C:35](B(O)O)=[CH:34][CH:33]=[CH:32][N:31]=1>O1CCOCC1.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:1]12([CH2:11][O:12][C:13]3[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][C:14]=3[C:35]3[C:30]([O:29][CH3:28])=[N:31][CH:32]=[CH:33][CH:34]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2762709(2-Methoxypyridin-3-yl)boronic acidHCID 867028434-(Adamantan-1-ylmethoxy)-3-bromobenzonitrile

Product 1

HCID 867028444-(Adamantan-1-ylmethoxy)-3-(2-methoxypyridin-3-yl)benzonitrileYield 98.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A reaction mixture of 4-(adamantan-1-ylmethoxy)-3-bromobenzonitrile (1.04 g, 3.00 mmol), potassium carbonate (1.00 g, 7.20 mmol) and (2-methoxypyridin-3-yl)boronic acid (0.92 g, 6.00 mmol) in dioxane (30 mL) was degassed three times with nitrogen, then tetrakis(triphenylphosphine)palladium(0) (0.18 g, 0.15 mmol) was added and the reaction mixture was degassed three further times with nitrogen. The resulting mixture was heated at 90° C. for 19 h, and then the reaction was cooled to ambient temperature, (2-methoxypyridin-3-yr)boronic acid (0.46 g, 3.00 mmol) and tetrakis(triphenylphosphfne)-pailadium(0) (0.09 g, 0.08 mmol) were added and the reaction was degassed three times with nitrogen and heated at 90° C. for further 7 h. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate (200 mL) and washed with water and brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (15% ethyl acetate in hexanes) afforded the title compound as a colorless solid (1.11 g, 98%): 1H NMR (300 MHz, CDCl3) δ 8.20-8.16 (m, 1H), 7.62-7.48 (m, 3H), 6.96-6.91 (m, 2H), 3.87 (s, 3H), 3.48 (s, 2H), 1.89 (br s, 3H), 1.68-1.35 (m, 12H); MS (ES+) m/z: 375.2, (M+1).

Workup

  1. customwas degassed three times with nitrogen
  2. customthe reaction mixture was degassed three further times with nitrogen
  3. temperaturethe reaction was cooled to ambient temperature
  4. customthe reaction was degassed three times with nitrogen
  5. temperatureheated at 90° C. for further 7 h
  6. temperatureAfter cooling to ambient temperature
  7. additionthe reaction mixture was diluted with ethyl acetate (200 mL)
  8. washwashed with water and brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by column chromatography (15% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-a493295be30048ae92b83ae3ef84dba0
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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