1-(Difluoromethoxy)-4-iodobenzene → HCID 67537639, compound

HRID 2241009Notes

Reaction equation

HRID 2241009 reaction equation
[F:1][CH:2]([F:15])[CH2:3][CH2:4][O:5][C:6]1[CH:11]=[C:10]([C:12]#[CH:13])[CH:9]=[CH:8][C:7]=1[F:14].I[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH:24]([F:26])[F:25])=[CH:19][CH:18]=1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.O>[F:25][CH:24]([F:26])[O:23][C:20]1[CH:21]=[CH:22][C:17]([C:13]#[C:12][C:10]2[CH:9]=[CH:8][C:7]([F:14])=[C:6]([O:5][CH2:4][CH2:3][CH:2]([F:1])[F:15])[CH:11]=2)=[CH:18][CH:19]=1

Participants

6

Reactant 2

HCID 27370081-(Difluoromethoxy)-4-iodobenzeneHCID 86627700HCID 86627700, compound

Product 1

HCID 67537639HCID 67537639, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
37.5 °C

Procedure

To a mixture of 2-(3,3-difluoropropoxy)-4-ethynyl-1-fluorobenzene (700 mg, 3.27 mmol) from the previous step, TEA (1.82 g, 2.5 mL, 17.99 mmol), PdCl2(PPh3)2 (114 mg, 0.163 mmol), and CuI (19 mg, 0.098 mmol) was added 4-iodo(difluoromethoxy)benzene (707 mg, 2.61 mmol). The reaction mixture was heated at 35-40° C. for 1 h under nitrogen. The reaction mixture was cooled to room temperature then poured into water. The aqueous mixture was extracted with EtOAc three times and the combined organic layers were dried over Na2SO4, filtered, and concentrated onto 10 g Celite. Flash chromatography (SiO2, 1% EtOAc 99% Hexanes to 5:95 EtOAc:Hexanes) provided 738 mg, 79%, of the title compound as a light yellow oil.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe aqueous mixture was extracted with EtOAc three times
  3. dry with materialthe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated onto 10 g Celite
  6. customFlash chromatography (SiO2, 1% EtOAc 99% Hexanes to 5:95 EtOAc:Hexanes) provided 738 mg, 79%

Sources & evidence

ORD record
ord-4a0e9a18f89a460b92f9464fda74958e
Source dataset
uspto-grants-2010_05
Patent number
US07723368B2

Reaction notes

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