Toluene → 4-Chloro-2-(3-chlorophenyl)-6-cyclopropylpyridine

HRID 1508807Notes

Reaction equation

HRID 1508807 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([CH:9]2[CH2:11][CH2:10]2)[N:3]=1.[Cl:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1(C)C=CC=CC=1>O.ClCCl.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.CCO>[Cl:8][C:6]1[CH:5]=[C:4]([CH:9]2[CH2:11][CH2:10]2)[N:3]=[C:2]([C:17]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:12])[CH:18]=2)[CH:7]=1

Participants

9

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 901122042,4-Dichloro-6-cyclopropylpyridine

Product 1

HCID 901124124-Chloro-2-(3-chlorophenyl)-6-cyclopropylpyridineYield 20%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A 250-mL round bottomed flask was charged with 2,4-dichloro-6-cyclopropylpyridine (1.08 g, 5.74 mmol), (3-chlorophenyl)boronic acid (0.99 g, 6.32 mmol), tetrakis(triphenylphosphine)palladium(0) (0.332 g, 0.28 mmol), and Cs2CO3 (5.61 g, 17.2 mmol). Toluene (40 ml), EtOH (10 ml) and water (20 ml) were added. The resulting mixture was stirred under Ar at 90° C. for 23 h. After cooling to room temperature, the reaction mixture was diluted with water (50 mL) and dichloromethane (50 mL). The mixture was filtered through celite washing solids with dichloromethane. The aqueous layer was separated and extracted with dichloromethane (2×50 mL). The combined organic extract was washed with saturated sodium chloride (25 mL) then dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica using hexane/dichloromethane (100:0 to 0:100) as eluent to afford the title compound (0.30 g, 20%) as a colorless oil. MW=264.15. 1H NMR (CDCl3, 500 MHz) δ 7.98-7.96 (m, 1H), 7.85-7.80 (m, 1H), 7.45 (d, J=1.5 Hz, 1H), 7.39-7.35 (m, 2H), 7.12 (d, J=1.5 Hz, 1H), 2.18-2.01 (m, 1H), 1.18-1.12 (m, 2H), 1.06-1.00 (m, 2H).

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationThe mixture was filtered
  3. washthrough celite washing solids with dichloromethane
  4. customThe aqueous layer was separated
  5. extractionextracted with dichloromethane (2×50 mL)
  6. extractionThe combined organic extract
  7. washwas washed with saturated sodium chloride (25 mL)
  8. dry with materialthen dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by chromatography on silica

Sources & evidence

ORD record
ord-4d7872c27ac54367849cbdacd34b836c
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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