1-(Prop-2-yn-1-yl)piperidin-4-ol → methyl (E)-[4-[3-(4-chlorophenyl)-3-[4-[3-(4-hydroxypiperidin-1-yl)propynyl]phenyl]allyloxy]-2-methylphenoxy]acetate

HRID 549885Notes

Reaction equation

HRID 549885 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]#[CH:10])[CH2:4][CH2:3]1.[Cl:11][C:12]1[CH:17]=[CH:16][C:15](/[C:18](/[C:35]2[CH:40]=[CH:39][C:38](I)=[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>O1CCCC1.C(N(CC)CC)C.C1C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[Cl:11][C:12]1[CH:13]=[CH:14][C:15](/[C:18](/[C:35]2[CH:36]=[CH:37][C:38]([C:10]#[C:9][CH2:8][N:5]3[CH2:6][CH2:7][CH:2]([OH:1])[CH2:3][CH2:4]3)=[CH:39][CH:40]=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:16][CH:17]=1

Participants

8

Reactant 2

HCID 186167231-(Prop-2-yn-1-yl)piperidin-4-olHCID 86629280methyl (Z)-[4-[3-(4-chlorophenyl)-3-(4-iodophenyl)allyloxy]-2-methylphenoxy]acetate

Product 1

HCID 86629312methyl (E)-[4-[3-(4-chlorophenyl)-3-[4-[3-(4-hydroxypiperidin-1-yl)propynyl]phenyl]allyloxy]-2-methylphenoxy]acetate

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 241BenzeneSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

4-Hydroxy-1-propargylpiperidine (280 mg, 2.01 mmol) was added under nitrogen atmosphere to a degassed solution of methyl (Z)-[4-[3-(4-chlorophenyl)-3-(4-iodophenyl)allyloxy]-2-methylphenoxy]acetate (450 mg, 0.82 mmol; prepared as described in example 7) in a mixture of tetrahydrofuran (10 mL) and triethylamine (8 mL) The solution was cooled to 0° C.; tetrakis(triphenylphosphine)palladium (85 mg, 0.073 mmol) and copper(I) iodide (22 mg, 0.115 mmol) were added. The reaction mixture was stirred at ambient temperature for 72 h, diluted with benzene (100 mL), decanted and evaporated in vacuo. The residue was purified by column chromatography (silica gel Fluka 60, benzene/methanol 10:0-4:6) yielding methyl (E)-[4-[3-(4-chlorophenyl)-3-[4-[3-(4-hydroxypiperidin-1-yl)propynyl]phenyl]allyloxy]-2-methylphenoxy]acetate.

Workup

  1. customdecanted
  2. customevaporated in vacuo
  3. customThe residue was purified by column chromatography (silica gel Fluka 60, benzene/methanol 10:0-4:6)

Sources & evidence

ORD record
ord-1f07485425d949fe9dcf4d861ec12ee5
Source dataset
uspto-grants-2011_05
Patent number
US07943613B2

Reaction notes

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