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

HRID 1810688
Notes
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Reaction equation

HRID 1810688 reaction equation
[CH2:1]([N:4]1[CH2:9][CH2:8][CH:7]([OH:10])[CH2:6][CH2:5]1)[C:2]#[CH:3].I[C:12]1[CH:17]=[CH:16][C:15](/[C:18](/[C:35]2[CH:40]=[CH:39][C:38]([S:41][C:42]([F:45])([F:44])[F:43])=[CH:37][CH:36]=2)=[CH:19]\[CH2:20][O:21][C:22]2[CH:33]=[CH:32][C:25]([O:26][CH2:27][C:28]([O:30][CH3:31])=[O:29])=[C:24]([CH3:34])[CH:23]=2)=[CH:14][CH:13]=1.C(NC(C)C)(C)C>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:12]2[CH:13]=[CH:14][C:15](/[C:18](/[C:35]3[CH:36]=[CH:37][C:38]([S:41][C:42]([F:44])([F:43])[F:45])=[CH:39][CH:40]=3)=[CH:19]\[CH2:20][O:21][C:22]3[CH:33]=[CH:32][C:25]([O:26][CH2:27][C:28]([O:30][CH3:31])=[O:29])=[C:24]([CH3:34])[CH:23]=3)=[CH:16][CH:17]=2)[CH2:5][CH2:6]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 186167231-(Prop-2-yn-1-yl)piperidin-4-olHCID 86629321methyl (Z)-[4-[3-(4-iodophenyl)-3-[4-(trifluoromethyl-sulfanyl)phenyl]allyloxy]-2-methyl-phenoxy]-acetate

Product 1

HCID 86629320methyl (E)-[4-[3-[4-[3-(4-hydroxypiperidin-1-yl)propynyl]phenyl]-3-[4-(trifluoromethylsulfanyl)phenyl]-allyloxy]-2-methylphenoxy]acetate

Reagents, catalysts & solvents 3

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

Procedure

1-Propargylpiperidin-4-ol (154 mg, 1.10 mmol) was added to a solution of methyl (Z)-[4-[3-(4-iodophenyl)-3-[4-(trifluoromethyl-sulfanyl)phenyl]allyloxy]-2-methylphenoxy]-acetate (340 mg, 0.553 mmol; prepared as described in example 56) and diisopropylamine (0.35 mL, 2.49 mmol) in tetrahydrofuran (9 mL). The mixture was degassed and copper(I) iodide (8.4 mg, 0.044 mmol) and bis(triphenylphosphine)palladium(II) dichloride (19.3 mg, 0.027 mmol) were added. The reaction mixture was stirred under argon at ambient temperature for 20 h, filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography (silica gel Fluka 60, chloroform/methanol 97:3) yielding methyl (E)-[4-[3-[4-[3-(4-hydroxypiperidin-1-yl)propynyl]phenyl]-3-[4-(trifluoromethylsulfanyl)phenyl]-allyloxy]-2-methylphenoxy]acetate.

Workup

  1. customThe mixture was degassed
  2. filtrationfiltered
  3. customthe filtrate was evaporated in vacuo
  4. customThe residue was purified by flash column chromatography (silica gel Fluka 60, chloroform/methanol 97:3)

Sources & evidence

ORD record
ord-16364e4ed51445d282fa92db1b9d203a
Source dataset
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08362016B2

Reaction notes

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