Sodium Carbonate → 2-Chloro-4-(5-chloro-2-methoxyphenyl)pyridine

HRID 1692349Notes

Reaction equation

HRID 1692349 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10](I)[CH:9]=1.[Cl:17][C:18]1[CH:23]=[C:22](B(O)O)[CH:21]=[CH:20][N:19]=1>C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.COCCOC>[Cl:17][C:18]1[CH:23]=[C:22]([C:10]2[CH:9]=[C:8]([Cl:7])[CH:13]=[CH:12][C:11]=2[O:14][CH3:15])[CH:21]=[CH:20][N:19]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 28009784-Chloro-2-iodoanisoleHCID 51515952-Chloropyridine-4-boronic acid

Product 1

HCID 594364732-Chloro-4-(5-chloro-2-methoxyphenyl)pyridine

Reagents, catalysts & solvents 2

HCID 178419050HCID 178419050, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a nitrogen purged aqueous solution of sodium carbonate (2M, 14 mL) and ethylene glycol dimethyl ether (25 mL) was added 4-chloro-2-iodoanisole (2.50 g, 0.00931 mol), 2-chloropyridine-4-boronic acid (1.61 g, 0.0102 mol) and bis(triphenylphosphine)palladium (II) dichloride (327 mg, 0.00047 mol). The reaction mixture was warmed to 50° C. and stirred for 5 hours. Following LCMS analysis the reaction was warmed to 75° C. and stirred for 5 hours before cooling to room temperature. The reaction was partitioned between ethyl acetate (100 mL) and a 10% w/v aqueous solution of citric acid (50 mL). The organic layer was washed with water (50 mL), dried over anhydrous magnesium sulphate, filtered and the solvents removed in vacuo to give the crude product as an orange oil (2.95 g). The material was purified using an ISCO™ companion (120 g column, eluting with 100% heptane to 7:3 heptane/ethyl acetate). Fractions containing product were combined and concentrated in vacuo to obtain the title compound as an off white solid (1.10 g).

Workup

  1. temperatureFollowing LCMS analysis the reaction was warmed to 75° C.
  2. stirringstirred for 5 hours
  3. temperaturebefore cooling to room temperature
  4. customThe reaction was partitioned between ethyl acetate (100 mL)
  5. washThe organic layer was washed with water (50 mL)
  6. dry with materialdried over anhydrous magnesium sulphate
  7. filtrationfiltered
  8. customthe solvents removed in vacuo
  9. customto give the crude product as an orange oil (2.95 g)
  10. customThe material was purified
  11. washan ISCO™ companion (120 g column, eluting with 100% heptane to 7:3 heptane/ethyl acetate)
  12. additionFractions containing product
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-236dd2e9357c47dd99a13d8077d537f8
Source dataset
uspto-grants-2012_04
Patent number
US08153814B2

Reaction notes

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