Cesium carbonate → Methyl [5-(4-ethylphenyl)pyridin-3-yl]carbamate

HRID 876228Notes

Reaction equation

HRID 876228 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][CH3:15])=[CH:10][CH:9]=2)[CH:7]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].[C:64](=[O:68])([O:66][CH3:67])[NH2:65]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].ClCCl>[CH2:14]([C:11]1[CH:12]=[CH:13][C:8]([C:6]2[CH:7]=[C:2]([NH:65][C:64](=[O:68])[O:66][CH3:67])[CH:3]=[N:4][CH:5]=2)=[CH:9][CH:10]=1)[CH3:15]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 11722Methyl CarbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2×HCID 665205743-Bromo-5-(4-ethylphenyl)pyridine

Product 1

HCID 68074774Methyl [5-(4-ethylphenyl)pyridin-3-yl]carbamate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
90 °C

Procedure

Under argon and at RT, a solution of 16.8 g (64 mmol) of 3-bromo-5-(4-ethylphenyl)pyridine in 70 ml of dioxane was added to a suspension of 555 mg (0.96 mmol, 0.015 eq.) of Xantphos (4,5-bis(diphenylphosphino)-9,9′-dimethylxanthene), 293 mg (0.32 mmol, 0.005 eq.) of tris(dibenzylideneacetone)dipalladium, 29.1 g (89 mmol, 1.4 eq.) of caesium carbonate and 5.8 g (77 mmol, 1.2 eq.) of methyl carbamate in 100 ml of dioxane. The reaction mixture was stirred at 90° C. for 20 h. Since the progress of the reaction was slow, a little at a time, three times in total, 555 mg (0.96 mmol, 0.015 eq.) of Xantphos and 293 mg (0.32 mmol, 0.005 eq.) of tris(dibenzylideneacetone)dipalladium were added to the reaction mixture, and in each case the mixture was stirred at 90° C. overnight. After addition of dichloromethane, the reaction mixture was filtered through Celite and the filtrate was concentrated under reduced pressure. The crude product was stirred with acetonitrile and the residue that remained was repeatedly washed with cold acetonitrile and dried under reduced pressure. Yield: 15 g (90% of theory)

Workup

  1. stirringin each case the mixture was stirred at 90° C. overnight
  2. filtrationthe reaction mixture was filtered through Celite
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. stirringThe crude product was stirred with acetonitrile
  5. washthe residue that remained was repeatedly washed with cold acetonitrile
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-4a94d15c41cf431cb40255f66939bf05
Source dataset
uspto-grants-2015_03
Patent number
US08987248B2

Reaction notes

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