3-Butyn-2-ol → 4-(1-Phenyl-1-(3-hydroxy-1-butyn-1-yl)-methylene)-piperidine-1-carboxylic Acid Tert-Butyl Ester

HRID 606769Notes

Reaction equation

HRID 606769 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)I)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.[CH3:38][CH:39]([OH:42])[C:40]#[CH:41]>C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.[Cu]I.N1CCCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:41]#[C:40][CH:39]([OH:42])[CH3:38])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 162393-Butyn-2-olHCID 521585Tris(furan-2-yl)phosphaneHCID 670465554-(1-Phenyl-1-iodomethylene)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 866219574-(1-Phenyl-1-(3-hydroxy-1-butyn-1-yl)-methylene)-piperidine-1-carboxylic Acid Tert-Butyl EsterYield 73.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 498840Bis(benzonitrile)palladium chlorideCatalystHCID 8082PiperidineSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 4-(1-phenyl-1-iodomethylene)-piperidine-1-carboxylic acid tert-butyl ester (0.537 g, 1.60 mmol), PdCl2(PhCN)2 (0.032 g, 0.083 mmol), tri-2-furylphosphine (0.0806 g, 0.347 mmol), and CuI (0.034 g, 0.178 mmol) was added piperidine (10 mL), followed by 3-butyn-2-ol (0.25 mL, 3.19 mmol). The mixture was heated at 100° C. for 8 h and then the solvent was removed in vacuo. The residue was partitioned with EtOAc-H2O and the aqueous phase was separated and re-extracted with EtOAc (×2). The combined organic layers were washed (H2O, brine), dried (Na2SO4) and concentrated, and the residue was purified by flash chromatography (SiO2/hexane:EtOAc, 3:2) to give the title compound (0.402 g, 73%) as a yellow orange oil which solidified on standing:

Workup

  1. customthe solvent was removed in vacuo
  2. customThe residue was partitioned with EtOAc-H2O
  3. customthe aqueous phase was separated
  4. extractionre-extracted with EtOAc (×2)
  5. washThe combined organic layers were washed (H2O, brine)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customthe residue was purified by flash chromatography (SiO2/hexane:EtOAc, 3:2)

Sources & evidence

ORD record
ord-64d6370bcc6045eaae67171ed67e044f
Source dataset
uspto-grants-2011_03
Patent number
US07915283B2

Reaction notes

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