Cesium carbonate → (2-Boc-amino-pyridin-4-yl)-acetic acid ethyl ester

HRID 911070Notes

Reaction equation

HRID 911070 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:5]=[CH:4][N:3]=1.[C:14](=[O:21])([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[NH2:15].C(=O)([O-])[O-].[Cs+].[Cs+]>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].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[C:17]([O:16][C:14]([NH:15][C:2]1[CH:7]=[C:6]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:5]=[CH:4][N:3]=1)=[O:21])([CH3:20])([CH3:19])[CH3:18]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 57709236Ethyl 2-(2-chloropyridin-4-yl)acetate

Product 1

HCID 53419364(2-Boc-amino-pyridin-4-yl)-acetic acid ethyl esterYield 74.1%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A flask was charged with ethyl 2-(2-chloropyridin-4-yl)acetate (20.00 g, 100.2 mmol), tert-butyl carbamate (35.21 g, 300.5 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (2.90 g, 5.01 mmol), tris(dibenzylideneacetone)dipalladium(0) (2.29 g, 2.51 mmol), cesium carbonate (48.96 g, 150 mmol) and THF (400 mL). The mixture was heated at reflux under nitrogen for 24 hours. Upon cooling, the reaction was quenched with 10% ammonium acetate solution and extracted with ethyl acetate. The combined organic extracts were washed with water and brine, dried and concentrated. The residue was purified by silica gel chromatography, eluting with 20% ethyl acetate/hexane to yield 20.80 g (72.6% yield) of the desired product as white solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux under nitrogen for 24 hours
  3. temperatureUpon cooling
  4. customthe reaction was quenched with 10% ammonium acetate solution
  5. extractionextracted with ethyl acetate
  6. washThe combined organic extracts were washed with water and brine
  7. customdried
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with 20% ethyl acetate/hexane

Sources & evidence

ORD record
ord-ec08aa2da8194aef8b5893c95d109547
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

Loading…