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

HRID 2069064Notes

Reaction equation

HRID 2069064 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8](C)(C)[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:5]=[CH:4][N:3]=1.C([NH:20][C:21](=[O:23])[O-:22])(C)(C)C.[CH3:24][C:25]1(C)[C:51]2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=C[C:26]1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.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]>[C:25]([O:22][C:21]([NH:20][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:23])([CH3:51])([CH3:26])[CH3:24]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 21252905Tert-butylcarbamateHCID 58532559HCID 58532559, compound

Product 1

HCID 53419364(2-Boc-amino-pyridin-4-yl)-acetic acid ethyl esterYield 852.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of ethyl 2-(2-chloropyridin-4-yl)-2-methylpropanoate (57) (2.80 g, 12.3 mmol), tert-butylcarbamate (4.32 g, 36.9 mmol), Pd2(dba)3 (281 mg, 0.307 mmol), Xantphos (355 mg, 0.615 mmol) and caesium carbonate (6.01 g, 18.5 mmol) in THF (10.0 mL) was purged with nitrogen and then stirred at 65° C. for 72 hr. The mixture was cooled to RT and was diluted with water and extracted with ether. The organic layer was washed with water and brine and then dried (MgSO4), and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 120 g, 5-8% EtOAc in isohexane, gradient elution) to give the title compound (58) (1.47 g, 37%): m/z 309 (M+H)+ (ES+)

Workup

  1. customwas purged with nitrogen
  2. temperatureThe mixture was cooled to RT
  3. additionwas diluted with water
  4. extractionextracted with ether
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried (MgSO4)
  7. customevaporated in vacuo
  8. customThe residue was purified by flash column chromatography (SiO2, 120 g, 5-8% EtOAc in isohexane, gradient elution)

Sources & evidence

ORD record
ord-1d684c10cc124a7394299e38812c64b3
Source dataset
uspto-grants-2012_10
Patent number
US08299073B2

Reaction notes

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