Triethylamine → 3-Chloro-5-(3-chloro-4-fluorophenylethynyl)-pyridine

HRID 606937Notes

Reaction equation

HRID 606937 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:8]#[CH:9])[CH:7]=1.[Cl:10][C:11]1[CH:16]=[C:15](I)[CH:14]=[CH:13][C:12]=1[F:18].C(N(CC)CC)C>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:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:8]#[C:9][C:15]2[CH:14]=[CH:13][C:12]([F:18])=[C:11]([Cl:10])[CH:16]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27246052-Chloro-1-fluoro-4-iodobenzeneHCID 235008873-Chloro-5-ethynylpyridine

Product 1

HCID 670477273-Chloro-5-(3-chloro-4-fluorophenylethynyl)-pyridineYield 71%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
60 °C

Procedure

Add bis(triphenylphosphine)palladium (II) dichloride (64 mg, 0.091 mmol), copper (I) iodide (35 mg, 0.18 mmol), and 3-chloro-5-ethynylpyridine, (prepared as described in PREPARATION 27), (250 mg, 1.8 mmol) to a solution of 2-chloro-1-fluoro -4-iodobenzene (560 mg, 2.2 mmol) in triethylamine (3.8 mL, 27 mmol) and heat at 60° C. for 5 h. Cool to room temperature and concentrate. Purify by silica gel chromatography, eluting with 50:50 to 100:0 dichloromethane:hexanes, followed by a second silica gel chromatography, eluting with 100:0 to 90:10 hexanes:ethyl acetate, to give the title compound as a white solid (340 mg, 70%).

Workup

  1. temperatureCool to room temperature
  2. concentrationconcentrate
  3. customPurify by silica gel chromatography
  4. washeluting with 50:50 to 100:0 dichloromethane
  5. washeluting with 100:0 to 90:10 hexanes

Sources & evidence

ORD record
ord-29627e92ed6e4a8c893f2e1b5633662b
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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