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

HRID 2069050Notes

Reaction equation

HRID 2069050 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([NH:18][C:19](=[O:21])[O-:20])(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:28][C:29]1(C)[C:55]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:30]1=2>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:29]([O:20][C:19]([NH:18][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])([CH3:55])([CH3:30])[CH3:28]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 21252905Tert-butylcarbamateHCID 57709236Ethyl 2-(2-chloropyridin-4-yl)acetate

Product 1

HCID 53419364(2-Boc-amino-pyridin-4-yl)-acetic acid ethyl esterYield 51%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of ethyl 2-(2-chloropyridin-4-yl)acetate (44) (15.0 g, 75.0 mmol), tert-butylcarbamate (26.4 g, 225 mmol), Pd2(dba)3 (1.719 g, 1.88 mmol), caesium carbonate (36.7 g, 113 mmol) and Xantphos® (2.17 g, 3.76 mmol) in THF (100 mL) was purged with nitrogen and was then stirred at 65° C. for 8 hr. The mixture was cooled to RT and was diluted with water and extracted with ether. The ether extracts were combined and washed with water and brine and then dried (MgSO4), and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 330 g, 5-20% EtOAc in isohexane, gradient elution) then subjected to SCX capture and release to provide the title compound (45) (12.0 g, 51%): m/z 281 (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. washwashed with water and brine
  6. dry with materialdried (MgSO4)
  7. customevaporated in vacuo
  8. customThe residue was purified by flash column chromatography (SiO2, 330 g, 5-20% EtOAc in isohexane, gradient elution)

Sources & evidence

ORD record
ord-304c5b653cc14b8fb84bee22548b805f
Source dataset
uspto-grants-2012_10
Patent number
US08299073B2

Reaction notes

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