Toluene → HCID 90112032, compound

HRID 1508688Notes

Reaction equation

HRID 1508688 reaction equation
Cl[CH:2]1[CH:7]=[C:6]([Cl:8])[C:5]([CH2:9][CH3:10])=[C:4]([CH3:11])[NH: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.[K+].[K+].C1(C)C=CC=CC=1>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.O.CCO>[Cl:8][C:6]1[CH:7]=[C:2]([C:17]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:12])[CH:18]=2)[N:3]=[C:4]([CH3:11])[C:5]=1[CH2:9][CH3:10]

Participants

8

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 90110589HCID 90110589, compound

Product 1

HCID 90112032HCID 90112032, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A 50-mL round bottomed flask was charged with 2,4-dichloro-5-ethyl-6-methyl-1,2-dihydropyridine (94 mg, 0.49 mmol, 1 eq.), (3-chlorophenyl)boronic acid (77 mg, 0.49 mmol, 1 eq.), tetrakis(triphenylphosphine)palladium(0) (50 mg, 0.09 mmol, 0.09 eq.), and K2CO3 (200 mg, 1.45 mmol, 3 eq.). Toluene (4 ml), EtOH (1.6 ml) and water (1.6 ml) were added. The resulting mixture was stirred under Ar at 90° C. for 3 hr. until the starting chloride was consumed. After cooling to room temperature, the aqueous layer was separated and the organic layer was concentrated on a rotary evaporator. The residue was purified by chromatography on silica gel using hexane/dichloromethane (49:1, then 9:1 and 8:1) as eluent to afford 4-chloro-6-(3-chlorophenyl)-3-ethyl-2-methyl-pyridine, which was converted into its corresponding HCl salt by treating with 4N HCl in dioxane (120 mg, 81% yield).

Workup

  1. customuntil the starting chloride was consumed
  2. temperatureAfter cooling to room temperature
  3. customthe aqueous layer was separated
  4. concentrationthe organic layer was concentrated on a rotary evaporator
  5. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-4f3cb95a93f54bfa8646a0f87e0b043e
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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