1,3-Dimethoxy-2-fluoro-4-iodobenzene → 4-(3-Fluoro-2,4-dimethoxyphenylethynyl)-1-(4-methoxybenzyl)-1H-pyrazole

HRID 2059616Notes

Reaction equation

HRID 2059616 reaction equation
[F:1][C:2]1[C:3]([O:11][CH3:12])=[C:4](I)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[C:13]([C:15]1[CH:16]=[N:17][N:18]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[CH:19]=1)#[CH:14]>CC#N.CCN(CC)CC.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>[F:1][C:2]1[C:3]([O:11][CH3:12])=[C:4]([C:14]#[C:13][C:15]2[CH:16]=[N:17][N:18]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)[CH:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]

Participants

6

Reactant 2

HCID 509982281,3-Dimethoxy-2-fluoro-4-iodobenzeneHCID 574219374-Ethynyl-1-(4-methoxybenzyl)-1H-pyrazole

Product 1

HCID 574219494-(3-Fluoro-2,4-dimethoxyphenylethynyl)-1-(4-methoxybenzyl)-1H-pyrazole

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

To a stirred solution of 3-fluoro-2,4-dimethoxy-iodobenzene (200 mg, 0.71 mmol) and 4-ethynyl-1-(4-methoxy-benzyl)-1H-pyrazole (180 mg, 0.85 mmol) in dry MeCN (4 ml) and NEt3 (2 ml) was added Pd(Ph3P)2Cl2 (15 mg, 3 mol %) and the reaction vessel was evacuated and backfilled with N2 (g) three times. Copper (I) iodide (6 mol %) was added and the reaction rapidly became dark. Stirring was continued at room temperature for 3 hours, then the crude mixture was concentrated directly onto silica-gel and purified by flash chromatography (silica-gel, eluted sequentially with hexanes:EtOAc, 3:1, 2:1) to give the product as a resin that crystallised slowly upon standing in the freezer (230 mg, 89%). 1H-NMR (300 MHz, CDCl3) δ 7.66 (s, 1H), 7.50 (s, 1H), 7.19 (d, J=8.6 Hz, 2H), 7.10 (dd, J=8.7, 2.1 Hz, 1H), 6.87 (d, J=8.6 Hz, 2H), 6.61 (t, J=8.2 Hz, 1H), 5.24 (s, 2H), 4.01 (s, 3H), 3.87 (s, 3H), 3.79 (s, 3H).

Workup

  1. customthe reaction vessel was evacuated
  2. additionCopper (I) iodide (6 mol %) was added
  3. customthe reaction rapidly became dark
  4. concentrationthe crude mixture was concentrated directly onto silica-gel
  5. custompurified by flash chromatography (silica-gel
  6. washeluted sequentially with hexanes
  7. customEtOAc, 3:1, 2:1) to give the product as a resin that
  8. customcrystallised slowly

Sources & evidence

ORD record
ord-07036981785548ab80d5a553eab1bbe9
Source dataset
uspto-grants-2012_10
Patent number
US08278290B2

Reaction notes

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