6-(5-Chloro-2,3-dihydrobenzofuran-7-yl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol → 2-(1-Benzenesulfonyl-5-bromo-1H-indol-2-ylmethyl)-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methylpentan-2-ol

HRID 400665Notes

Reaction equation

HRID 400665 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:11]([CH3:23])([CH3:22])[CH2:12][C:13]([C:18]([F:21])([F:20])[F:19])([OH:17])[CH2:14][C:15]#[CH:16])[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1.[Br:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][S:32]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)(=[O:34])=[O:33])=[C:27](I)[CH:26]=1>CN(C=O)C.C(N(CC)CC)C.[Cl-].[NH4+].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>[C:35]1([S:32]([N:31]2[C:28]3[C:29](=[CH:30][C:25]([Br:24])=[CH:26][CH:27]=3)[CH:16]=[C:15]2[CH2:14][C:13]([OH:17])([CH2:12][C:11]([C:4]2[C:5]3[O:9][CH2:8][CH2:7][C:6]=3[CH:10]=[C:2]([Cl:1])[CH:3]=2)([CH3:23])[CH3:22])[C:18]([F:21])([F:19])[F:20])(=[O:34])=[O:33])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

8

Reactant 2

HCID 469392166-(5-Chloro-2,3-dihydrobenzofuran-7-yl)-6-methyl-4-trifluoromethylhept-1-yn-4-olHCID 60026307N-(4-Bromo-2-iodophenyl)benzenesulfonamide

Product 1

HCID 600264582-(1-Benzenesulfonyl-5-bromo-1H-indol-2-ylmethyl)-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methylpentan-2-olYield 39.1%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 6-(5-chloro-2,3-dihydrobenzofuran-7-yl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol (170 mg, 0.49 mmol), N-(4-bromo-2-iodophenyl)benzenesulfonamide (220 mg, 0.50 mmol), dichlorobis(triphenylphosphine)palladium (II) (20 mg, 0.03 mmol), and copper (I) iodide (10 mg, 0.05 mmol) in 1 nL of DMF and 0.7 mL of triethylamine was warmed at 70° C. After 45 minutes, the mixture was cooled and diluted with 7 mL of saturated aqueous ammonium chloride solution and extracted with three 7 mL portions of ethyl acetate. The combined organic layers were washed with two 7 mL portions of saturated aqueous ammonium chloride solution, four 7 mL portions of brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude residue was purified on silica gel eluting with ethyl acetate-hexanes (0-30% gradient) to afford 126 mg (39% yield) of the title compound.

Workup

  1. temperaturethe mixture was cooled
  2. extractionextracted with three 7 mL portions of ethyl acetate
  3. washThe combined organic layers were washed with two 7 mL portions of saturated aqueous ammonium chloride solution, four 7 mL portions of brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified on silica gel eluting with ethyl acetate-hexanes (0-30% gradient)

Sources & evidence

ORD record
ord-a35cf86c4af3414da1993fce281260b4
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

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