Piperidine → Tert-butyl(4-chloro-2-{[2-methyl-5-(propylsulfonyl)phenyl]ethynyl}phenoxy)acetate

HRID 2390137Notes

Reaction equation

HRID 2390137 reaction equation
Br[C:2]1[CH:7]=[C:6]([S:8]([CH2:11][CH2:12][CH3:13])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[CH3:14].[C:15]([O:19][C:20](=[O:32])[CH2:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=1[C:30]#[CH:31])([CH3:18])([CH3:17])[CH3:16].N1CCCCC1>CCOC(C)=O.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:15]([O:19][C:20](=[O:32])[CH2:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=1[C:30]#[C:31][C:2]1[CH:7]=[C:6]([S:8]([CH2:11][CH2:12][CH3:13])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[CH3:14])([CH3:18])([CH3:17])[CH3:16]

Participants

6

Reactant 3

HCID 8082PiperidineHCID 56594381Tert-butyl(4-chloro-2-ethynylphenoxy)acetate2×HCID 585220912-Bromo-1-methyl-4-(propylsulfonyl)benzene2×

Product 1

HCID 58521875Tert-butyl(4-chloro-2-{[2-methyl-5-(propylsulfonyl)phenyl]ethynyl}phenoxy)acetate

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2-bromo-1-methyl-4-(propylsulfonyl)benzene (Intermediate 37; 14.86 g, 53.6 mmol), tert-butyl(4-chloro-2-ethynylphenoxy)acetate (Intermediate 3, 13.00 g; 48.7 mmol), dichlorobis(triphenylphosphine)palladium(II) (1.37 g; 1.95 mmol) and piperidine (14.5 mL) was heated at 70° C. for 18 hours. The reaction mixture was taken up in EtOAc, washed twice with ammonium chloride and once with brine. The organic phase was dried over MgSO4, filtered and concentrated to dryness affording a crude, which was purified by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc. The compound thus obtained as a brown sticky solid was recrystallized twice from EtOAc/petroleum ether to afford the title compound as a beige solid.

Workup

  1. washwashed twice with ammonium chloride and once with brine
  2. dry with materialThe organic phase was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. customaffording a crude, which
  6. customwas purified by flash column chromatography (silica)
  7. washeluting with cyclohexane containing
  8. temperatureincreasing amounts of EtOAc
  9. customThe compound thus obtained as a brown sticky solid
  10. customwas recrystallized twice from EtOAc/petroleum ether

Sources & evidence

ORD record
ord-27458ffdb07e4658b50be3bec3f780e0
Source dataset
uspto-grants-2012_09
Patent number
US08273769B2

Reaction notes

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