Diisopropylamine → methyl (Z)-[4-[3-(4-tert-butylphenyl]-3-[4-[3-(4-hydroxypiperidin-1-yl)propynyl]phenyl]allyloxy]-2-methylphenoxy]-acetate

HRID 1810680Notes

Reaction equation

HRID 1810680 reaction equation
[OH:1][CH:2]1CCN(CC#C)C[CH2:3]1.[CH:11](NC(C)C)(C)C.[C:18]([C:22]1[CH:27]=[CH:26][C:25](/[C:28](/[C:44]2[CH:49]=[CH:48][C:47]([C:50]#[C:51][CH2:52][N:53]3[CH2:58]CO[CH2:55][CH2:54]3)=[CH:46][CH:45]=2)=[CH:29]/[CH2:30][O:31][C:32]2[CH:42]=[CH:41][C:35]([O:36][CH2:37][C:38]([OH:40])=[O:39])=[C:34]([CH3:43])[CH:33]=2)=[CH:24][CH:23]=1)([CH3:21])([CH3:20])[CH3:19]>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>[C:18]([C:22]1[CH:27]=[CH:26][C:25](/[C:28](/[C:44]2[CH:49]=[CH:48][C:47]([C:50]#[C:51][CH2:52][N:53]3[CH2:54][CH2:55][CH:2]([OH:1])[CH2:3][CH2:58]3)=[CH:46][CH:45]=2)=[CH:29]/[CH2:30][O:31][C:32]2[CH:42]=[CH:41][C:35]([O:36][CH2:37][C:38]([O:40][CH3:11])=[O:39])=[C:34]([CH3:43])[CH:33]=2)=[CH:24][CH:23]=1)([CH3:21])([CH3:20])[CH3:19]

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 186167231-(Prop-2-yn-1-yl)piperidin-4-olHCID 23633559(Z)-[4-[3-(4-tert-Butylphenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methylphenoxy]acetic Acid

Product 1

HCID 86629316methyl (Z)-[4-[3-(4-tert-butylphenyl]-3-[4-[3-(4-hydroxypiperidin-1-yl)propynyl]phenyl]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

4-Hydroxy-1-propargylpiperidine (171 mg, 1.23 mmol) and diisopropylamine (0.40 mL, 2.85 mmol) were added to a solution of the methyl (Z)-[4-[3-(4-tert-butylphenyl)-3-(4-iodohenyl)llyloxy]-2-methylphenoxy]acetate (350 mg, 0.614 mmol; prepared as described in example 30) in tetrahydrofuran (10 mL). The mixture was degassed and copper(I) iodide (10 mg, 0.053 mmol) and bis(triphenylphosphine)palladium(II) dichloride (22 mg, 0.031 mmol) were added. The reaction mixture was stirred at ambient temperature over night, filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography (silica gel Fluka 60, dichloromethane/methanol 97:3) yielding methyl (Z)-[4-[3-(4-tert-butylphenyl]-3-[4-[3-(4-hydroxypiperidin-1-yl)propynyl]phenyl]allyloxy]-2-methylphenoxy]-acetate as white solid.

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, dichloromethane/methanol 97:3)

Sources & evidence

ORD record
ord-50a4d6a592ba4245a827a99fe5e49fd1
Source dataset
uspto-grants-2013_01
Patent number
US08362016B2

Reaction notes

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