Sodium Carbonate → 4-[(5-Chloro-6-isopropoxypyridin-3-yl)oxy]-3-(2-methoxypyridin-3-yl)benzonitrile

HRID 1620340Notes

Reaction equation

HRID 1620340 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][C:11]1[CH:12]=[N:13][C:14]([O:18][CH:19]([CH3:21])[CH3:20])=[C:15]([Cl:17])[CH:16]=1)[C:5]#[N:6].[CH3:22][O:23][C:24]1[C:29](B(O)O)=[CH:28][CH:27]=[CH:26][N:25]=1.C(=O)([O-])[O-].[Na+].[Na+]>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>[Cl:17][C:15]1[CH:16]=[C:11]([O:10][C:9]2[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=2[C:29]2[C:24]([O:23][CH3:22])=[N:25][CH:26]=[CH:27][CH:28]=2)[CH:12]=[N:13][C:14]=1[O:18][CH:19]([CH3:21])[CH3:20]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2762709(2-Methoxypyridin-3-yl)boronic acidHCID 666670393-Bromo-4-[(5-chloro-6-isopropoxypyridin-3-yl)oxy]benzonitrile

Product 1

HCID 666672584-[(5-Chloro-6-isopropoxypyridin-3-yl)oxy]-3-(2-methoxypyridin-3-yl)benzonitrileYield 77.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-bromo-4-[(5-chloro-6-isopropoxypyridin-3-yl)oxy]benzonitrile (Preparation 25, 638 mg, 1.74 mmol) and 2-methoxy-3-pyridylboronic acid (265 mg, 1.74 mmol) in dioxan (10.5 mL) was added a 1 M aqueous solution of sodium carbonate (5.2 mL, 5.21 mmol). The reaction was sparged with nitrogen before the addition of tetrakis(triphenylphosphine)palladium(0) (200 mg, 0.17 mmol). The reaction mixture was heated to 100° C. and stirred for 16 hours and then concentrated in vacuo The residue was partitioned between water (30 mL) and EtOAc (25 mL). The aqueous phase was separated and extracted with EtOAc (2×25 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford a yellow oil which was purified by silica gel column chromatography, eluting with 9:1 heptane/EtOAc. Fractions containing product were combined and concentrated in vacuo to obtain the title compound as a colourless oil (534 mg, 60%).

Workup

  1. concentrationconcentrated in vacuo The residue
  2. customwas partitioned between water (30 mL) and EtOAc (25 mL)
  3. customThe aqueous phase was separated
  4. extractionextracted with EtOAc (2×25 mL)
  5. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a yellow oil which
  9. customwas purified by silica gel column chromatography
  10. washeluting with 9:1 heptane/EtOAc
  11. additionFractions containing product
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-90d3f2ae10b449c6959b5e9f17fbf599
Source dataset
uspto-grants-2014_07
Patent number
US08772343B2

Reaction notes

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