Triethylamine → Methyl 4-{1,2-dimethyl-1-[4-(1-methyl-1-pyridin-2-ylethoxy)phenyl]propyl}benzoate

HRID 1025809Notes

Reaction equation

HRID 1025809 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:13]2[CH:28]=[CH:27][C:16]([O:17][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)([CH3:20])[CH3:19])=[CH:15][CH:14]=2)([CH3:12])[CH:9]([CH3:11])[CH3:10])=[CH:4][CH:3]=1.C(N(CC)CC)C.CN([CH:39]=[O:40])C.[CH3:41][OH:42]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:12][C:8]([C:5]1[CH:6]=[CH:7][C:2]([C:41]([O:40][CH3:39])=[O:42])=[CH:3][CH:4]=1)([C:13]1[CH:28]=[CH:27][C:16]([O:17][C:18]([CH3:20])([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)[CH3:19])=[CH:15][CH:14]=1)[CH:9]([CH3:11])[CH3:10]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 21901440N,N-dimethylformamide methanolHCID 583812252-(1-{4-[1-(4-Iodophenyl)-1,2-dimethylpropyl]phenoxy}-1-methylethyl)pyridine

Product 1

HCID 59026736Methyl 4-{1,2-dimethyl-1-[4-(1-methyl-1-pyridin-2-ylethoxy)phenyl]propyl}benzoate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
80 °C

Procedure

A stirred mixture of 5f (1 equiv), palladium (II) acetate (0.1 equiv.), 1,1′bis(diphenylphosphino)ferrocene (0.2 equiv) and triethylamine (2.4 equiv) in DMF/methanol (1:1) is purged with carbon monoxide for approximately 10 min and then heated to 80° C. under a carbon monoxide atmosphere (balloon). After completion of reaction, the reaction mixture is cooled to room temperature and then filtered through a short column of CELITE®, eluting copiously with EtOAc. The filtrate is poured into saturated aqueous sodium bicarbonate and extracted three times with EtOAc. The combined organic extracts are washed with water, brine, dried (Na2SO4) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel affords the title compound 5g.

Workup

  1. customis purged with carbon monoxide for approximately 10 min
  2. customAfter completion of reaction
  3. temperaturethe reaction mixture is cooled to room temperature
  4. filtrationfiltered through a short column of CELITE®
  5. washeluting copiously with EtOAc
  6. additionThe filtrate is poured into saturated aqueous sodium bicarbonate
  7. extractionextracted three times with EtOAc
  8. washThe combined organic extracts are washed with water, brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customPurification of the crude residue by flash chromatography on silica gel

Sources & evidence

ORD record
ord-46050621a08e400fb991f03100df28ca
Source dataset
uspto-grants-2014_05
Patent number
US08729104B2

Reaction notes

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