Triethylamine → 2-{4-[5-(4-Chlorophenyl)-3-fluoropyridin-2-ylethynyl]phenoxy}ethanol

HRID 734801Notes

Reaction equation

HRID 734801 reaction equation
I[C:2]1[CH:11]=[CH:10][C:5]([O:6][CH2:7][CH2:8][OH:9])=[C:4](C)[CH:3]=1.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:21]=[C:22]([F:28])[C:23]([C:26]#[CH:27])=[N:24][CH:25]=2)=[CH:16][CH:15]=1.C(N(CC)CC)C.CCOC(C)=O>C1COCC1.[Cu]I>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:21]=[C:22]([F:28])[C:23]([C:26]#[C:27][C:2]3[CH:3]=[CH:4][C:5]([O:6][CH2:7][CH2:8][OH:9])=[CH:10][CH:11]=3)=[N:24][CH:25]=2)=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 40551152-(4-Iodo-2-methyl-phenoxy)-ethanolHCID 600554165-(4-Chlorophenyl)-2-ethynyl-3-fluoropyridine

Product 1

HCID 690591092-{4-[5-(4-Chlorophenyl)-3-fluoropyridin-2-ylethynyl]phenoxy}ethanol

Reagents, catalysts & solvents 2

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

Procedure

Under an argon atmosphere 14.8 mg (0.078 mmol) of CuI was added to a solution of 0.82 g (3.11 mmol) of 2-(4-iodo-2-methylphenoxy)ethanol, 0.72 g (2.11 mmol) of 5-(4-chlorophenyl)-2-ethynyl-3-fluoropyridine, 57 mg (0.078 mmol) of [1,1′-bis(diphenylphosphine)ferrocene]palladium (II) chloride, and 0.86 mL (6.22 mmol) of triethylamine in 20 mL of THF and the mixture was stirred for 16 hours at RT. The reaction mixture was combined with EtOAc, and the precipitate was filtered off and washed with EtOAc. The filtrate and the organic washing solutions were washed with 5% aqueous ammonia and water, dried over magnesium sulfate and evaporated down in vacuo. The crude product was purified by column chromatography (silica gel, PE/EtOAc 1:1). Yield: 0.20 g (18% of theoretical); C21H15ClFNO2 (M=367.800); calc.: molpeak (M+H)+: 368/370 (Cl); found: molpeak (M+H)+: 368/370 (Cl); HPLC-MS: 5.94 minutes (method B).

Workup

  1. filtrationthe precipitate was filtered off
  2. washwashed with EtOAc
  3. washThe filtrate and the organic washing solutions were washed with 5% aqueous ammonia and water
  4. dry with materialdried over magnesium sulfate
  5. customevaporated down in vacuo
  6. customThe crude product was purified by column chromatography (silica gel, PE/EtOAc 1:1)
  7. custom5.94 minutes (method B)

Sources & evidence

ORD record
ord-c6a759317e344e57b093cec4e49c38ad
Source dataset
uspto-grants-2009_09
Patent number
US07592358B2

Reaction notes

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