Diisopropylamine → methyl (E)-[4-[3-[4-[3-(4-hydroxypiperidin-1-yl)propynyl]phenyl]-3-(3-trifluoromethylphenyl)allyloxy]-2-methylphenoxy]acetate

HRID 1810662Notes

Reaction equation

HRID 1810662 reaction equation
[CH2:1]([N:4]1[CH2:9][CH2:8][CH:7]([OH:10])[CH2:6][CH2:5]1)[C:2]#[CH:3].C(NC(C)C)(C)C.I[C:19]1[CH:24]=[CH:23][C:22](/[C:25](/[C:42]2[CH:47]=[CH:46][CH:45]=[C:44]([C:48]([F:51])([F:50])[F:49])[CH:43]=2)=[CH:26]\[CH2:27][O:28][C:29]2[CH:40]=[CH:39][C:32]([O:33][CH2:34][C:35]([O:37][CH3:38])=[O:36])=[C:31]([CH3:41])[CH:30]=2)=[CH:21][CH:20]=1>O1CCCC1.[Cu]I.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>[OH:10][CH:7]1[CH2:8][CH2:9][N:4]([CH2:1][C:2]#[C:3][C:19]2[CH:20]=[CH:21][C:22](/[C:25](/[C:42]3[CH:47]=[CH:46][CH:45]=[C:44]([C:48]([F:49])([F:50])[F:51])[CH:43]=3)=[CH:26]\[CH2:27][O:28][C:29]3[CH:40]=[CH:39][C:32]([O:33][CH2:34][C:35]([O:37][CH3:38])=[O:36])=[C:31]([CH3:41])[CH:30]=3)=[CH:23][CH:24]=2)[CH2:5][CH2:6]1

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 186167231-(Prop-2-yn-1-yl)piperidin-4-olHCID 86629302methyl (E)-[4-[3-(4-iodophenyl)-3-(3-trifluoromethylphenyl)allyloxy]-2-methylphenoxy]acetate

Product 1

HCID 86629303methyl (E)-[4-[3-[4-[3-(4-hydroxypiperidin-1-yl)propynyl]phenyl]-3-(3-trifluoromethylphenyl)allyloxy]-2-methylphenoxy]acetate

Reagents, catalysts & solvents 3

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

Procedure

1-Propargylpiperidin-4-ol (191 mg, 1.374 mmol) and diisopropylamine (0.45 mL, 3.23 mmol) were added to a solution of methyl (E)-[4-[3-(4-iodophenyl)-3-(3-trifluoromethylphenyl)-allyloxy]-2-methylphenoxy]acetate (400 mg, 0.687 mmol; prepared as described in example 34) in tetrahydrofuran (10 mL). The mixture was degassed and copper(I) iodide (10.4 mg, 0.055 mmol) and bis(triphenylphosphine)palladium(II) dichloride (24.1 mg, 0.034 mmol) were added. The reaction mixture was stirred at ambient temperature for 20 h and evaporated in vacuo. The residue was purified by flash column chromatography (silica gel Fluka 60, chloroform/methanol 96:4) yielding methyl (E)-[4-[3-[4-[3-(4-hydroxypiperidin-1-yl)propynyl]phenyl]-3-(3-trifluoromethylphenyl)allyloxy]-2-methylphenoxy]acetate as yellow oil.

Workup

  1. customThe mixture was degassed
  2. customevaporated in vacuo
  3. customThe residue was purified by flash column chromatography (silica gel Fluka 60, chloroform/methanol 96:4)

Sources & evidence

ORD record
ord-4fb0090adcba4229bcbaed367d60e66f
Source dataset
uspto-grants-2013_01
Patent number
US08362016B2

Reaction notes

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