Diisopropylamine → 2-[4-(5-Bromopyridin-2-ylethynyl)-2-methylphenoxy]ethanol

HRID 734789Notes

Reaction equation

HRID 734789 reaction equation
[C:1]([C:3]1[CH:12]=[CH:11][C:6]([O:7][CH2:8][CH2:9][OH:10])=[C:5]([CH3:13])[CH:4]=1)#[CH:2].Br[C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][N:16]=1.C(NC(C)C)(C)C>C1COCC1.[Cu]I>[Br:21][C:18]1[CH:19]=[CH:20][C:15]([C:2]#[C:1][C:3]2[CH:12]=[CH:11][C:6]([O:7][CH2:8][CH2:9][OH:10])=[C:5]([CH3:13])[CH:4]=2)=[N:16][CH:17]=1

Participants

6

Reactant 3

HCID 7912DiisopropylamineHCID 693532,5-DibromopyridineHCID 575658612-(4-Ethynyl-2-methylphenoxy)ethanol

Product 1

HCID 690586072-[4-(5-Bromopyridin-2-ylethynyl)-2-methylphenoxy]ethanol

Reagents, catalysts & solvents 2

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

Procedure

0.26 g (1.36 mmol) of CuI was added to a degassed solution of 11.98 g (68.00 mmol) of 2-(4-ethynyl-2-methylphenoxy)ethanol, 16.11 g (68.00 mmol) of 2,5-dibromopyridine, 0.96 g (1.36 mmol) of bis(triphenylphosphane)palladium (II) chloride, and 19.22 mL (136.00 mmol) of diisopropylamine in 500 mL of THF and the mixture was stirred for 4 hours at RT. The reaction mixture was evaporated down in vacuo and the residue taken up in 800 mL of EtOAc. The organic phase was with water and saturated aqueous NaCl solution washed, dried over sodium sulfate, and evaporated down in vacuo. The crude product was purified by column chromatography (silica gel, gradient DCM/EtOAc 90:10→80:20). Yield: 13.20 g (58% of theoretical); C16H14BrNO2 (M=332.192); calc.: molpeak (M+H)+: 332/334 (Br); found: molpeak (M+H)+: 332/334 (Br); Rf value: 0.39 (silica gel, cyc/EtOAc 1:1).

Workup

  1. customThe reaction mixture was evaporated down in vacuo
  2. washwashed
  3. dry with materialdried over sodium sulfate
  4. customevaporated down in vacuo
  5. customThe crude product was purified by column chromatography (silica gel, gradient DCM/EtOAc 90:10→80:20)

Sources & evidence

ORD record
ord-ea5cb6ad63444715a4a1454a4eed96ae
Source dataset
uspto-grants-2009_09
Patent number
US07592358B2

Reaction notes

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