Triethylamine → 3-Chloro-5-(3,4-difluorophenylethynyl)-pyridine

HRID 606887Notes

Reaction equation

HRID 606887 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:8]#[CH:9])[CH:7]=1.[F:10][C:11]1[CH:16]=[CH:15][C:14](I)=[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:14]2[CH:15]=[CH:16][C:11]([F:10])=[C:12]([F:18])[CH:13]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27244441,2-Difluoro-4-iodobenzeneHCID 235008873-Chloro-5-ethynylpyridine

Product 1

HCID 670477473-Chloro-5-(3,4-difluorophenylethynyl)-pyridineYield 88%

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 (49 mg, 0.07 mmol), copper (I) iodide (28 mg, 0.15 mmol), and 3-chloro-5-ethynylpyridine, (prepared as described in PREPARATION 27), (200 mg, 1.5 mmol) to a solution of 1,2-difluoro-4-iodobenzene (420 mg, 1.7 mmol) in triethylamine (3.1 mL, 22 mmol) and heat at 60° C. for 16 h. Cool to room temperature and concentrate. Purify the residue by silica gel chromatography, eluting with a gradient of 50:50 to 100:0 dichloromethane:hexanes, followed by a second silica gel chromatography, eluting with 95:5 to 85:15 hexanes:ethyl acetate to give the title compound as a white solid (320 mg, 88%).

Workup

  1. temperatureCool to room temperature
  2. concentrationconcentrate
  3. customPurify the residue by silica gel chromatography
  4. washeluting with a gradient of 50:50 to 100:0 dichloromethane
  5. washeluting with 95:5 to 85:15 hexanes

Sources & evidence

ORD record
ord-f6090631ab784926a8b054afdce6dcfd
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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