Acetonitrile → 6-(5-Fluoro-2-methylphenyl)-1-(3-fluoro-2-nitrophenyl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol

HRID 400663Notes

Reaction equation

HRID 400663 reaction equation
[F:1][C:2]1[C:3]([N+:16]([O-:18])=[O:17])=[C:4](OS(C(F)(F)F)(=O)=O)[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.C(#N)C.[F:29][C:30]1[CH:31]=[CH:32][C:33]([CH3:49])=[C:34]([C:36]([CH3:48])([CH3:47])[CH2:37][C:38]([C:43]([F:46])([F:45])[F:44])([OH:42])[CH2:39][C:40]#[CH:41])[CH:35]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.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.O1CCCC1>[F:29][C:30]1[CH:31]=[CH:32][C:33]([CH3:49])=[C:34]([C:36]([CH3:47])([CH3:48])[CH2:37][C:38]([C:43]([F:44])([F:45])[F:46])([OH:42])[CH2:39][C:40]#[C:41][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=2[N+:16]([O-:18])=[O:17])[CH:35]=1

Participants

9

Reactant 4

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 469390162-(1,1-Dimethyl-3-hydroxy-3-trifluoromethyl-5-hexynyl)-4-fluorotolueneHCID 600266203-Fluoro-2-nitrophenyl trifluoromethanesulphonate

Product 1

HCID 600264926-(5-Fluoro-2-methylphenyl)-1-(3-fluoro-2-nitrophenyl)-6-methyl-4-trifluoromethylhept-1-yn-4-olYield 45.3%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 67553Tetrabutylammonium IodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of trifluoromethanesulfonic acid 3-fluoro-2-nitrophenyl ester (149 mg, 0.52 mmol), dichlorobis(triphenylphosphine)palladium (II) (20 mg, 0.028 mmol), copper (I) iodide (14 mg, 0.074 mmol), tetrabutyl ammonium iodide (200 mg, 0.54 mmol), 0.25 mL of anhydrous triethylamine, 0.5 mL of anhydrous acetonitrile, and 0.5 mL of anhydrous tetrahydrofuran was stirred at room temperature for 30 minutes. The resulting mixture was treated with 6-(5-fluoro-2-methylphenyl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol (145 mg, 0.48 mmol) and stirred at room temperature for 18 hours. The crude product was purified by chromatography on SiO2 (50% hexanes in dichloromethane) to give 96 mg of the title product as light yellow oil, (45% yield).

Workup

  1. stirringstirred at room temperature for 18 hours
  2. customThe crude product was purified by chromatography on SiO2 (50% hexanes in dichloromethane)

Sources & evidence

ORD record
ord-e66f46184a51474db2757ffd1848176d
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

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