Triethylamine → 3-Chloro-5-(4-fluoro-3-methoxyphenylethynyl)-pyridine

HRID 606950Notes

Reaction equation

HRID 606950 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[O:9][CH3:10].C(N(CC)CC)C.[Cl:18][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([C:25]#[CH:26])[CH:24]=1>C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:18][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([C:25]#[C:26][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[C:3]([O:9][CH3:10])[CH:4]=2)[CH:24]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 235008873-Chloro-5-ethynylpyridineHCID 265982411-Fluoro-4-iodo-2-methoxybenzene

Product 1

HCID 670477813-Chloro-5-(4-fluoro-3-methoxyphenylethynyl)-pyridineYield 95.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalyst

Procedure

Dissolve 1-fluoro-4-iodo-2-methoxybenzene, (prepared as described in PREPARATION 47), (480 mg, 1.9 mmol) in triethylamine (7 mL, 53 mmol) and add 3-chloro-5-ethynylpyridine, (prepared as described in PREPARATION 27), (250 mg, 1.8 mmol) followed by bis(triphenylphosphine)palladium (II) dichloride (51 mg, 0.07 mmol) and copper (I) iodide (28 mg, 0.15 mmol). Stir for 18 h at room temperature, concentrate, and purify by silica gel chromatography, eluting with 3:1 hexanes:ethyl acetate. Further purify on silica gel, eluting with 100% dichloromethane, to give the title compound as a white solid (450 mg, 94%).

Workup

  1. concentrationconcentrate
  2. custompurify by silica gel chromatography
  3. washeluting with 3:1 hexanes
  4. customFurther purify on silica gel
  5. washeluting with 100% dichloromethane

Sources & evidence

ORD record
ord-609cc0c1b0a94dc48f8e0b644ad8ba5c
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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