Triethylamine → Tert-butyl{4-chloro-2-[(4-methylpyridin-3-yl)ethynyl]phenoxy}acetate

HRID 2390121Notes

Reaction equation

HRID 2390121 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[CH3:8].[C:9]([O:13][C:14](=[O:26])[CH2:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=1[C:24]#[CH:25])([CH3:12])([CH3:11])[CH3:10].C(N(CC)CC)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C1COCC1>[C:9]([O:13][C:14](=[O:26])[CH2:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=1[C:24]#[C:25][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[CH3:8])([CH3:12])([CH3:11])[CH3:10]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 8176303-Bromo-4-methylpyridineHCID 56594381Tert-butyl(4-chloro-2-ethynylphenoxy)acetate2×

Product 1

HCID 58521948Tert-butyl{4-chloro-2-[(4-methylpyridin-3-yl)ethynyl]phenoxy}acetate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 3-bromo-4-methylpyridine (Apollo; 355 mg; 2.06 mmol), tert-butyl(4-chloro-2-ethynylphenoxy)acetate (Intermediate 3, 500 mg; 1.87 mmol), dichlorobis(triphenylphosphine)palladium(II) (82 mg; 0.11 mmol), copper(I) iodide (21 mg; 0.11 mmol) was degassed during two minutes under nitrogen then THF (7.5 mL) and triethylamine (520 μL; 3.75 mmol) were added and reaction mixture was stirred at 60° C. for 16 hours. The solvents were removed under vacuum affording a dark brown residue, which was purified by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc. The title compound was obtained as a dark brown sticky solid.

Workup

  1. customwas degassed during two minutes under nitrogen
  2. customreaction mixture
  3. customThe solvents were removed under vacuum
  4. customaffording a dark brown residue, which
  5. customwas purified by flash column chromatography (silica)
  6. washeluting with cyclohexane containing
  7. temperatureincreasing amounts of EtOAc

Sources & evidence

ORD record
ord-8dfc4f7844f243e2a372e3758a0ac0ef
Source dataset
uspto-grants-2012_09
Patent number
US08273769B2

Reaction notes

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