Carbon Dioxide → Ethyl (6-aminopyridin-2-yl)acetate

HRID 1982677Notes

Reaction equation

HRID 1982677 reaction equation
CCCC[CH2:5][CH3:6].C([Li])CCC.C[Si](C)(C)[N:14]([C:19]1[N:24]=[C:23]([CH3:25])[CH:22]=[CH:21][CH:20]=1)[Si](C)(C)C.[C:28](=[O:30])=[O:29]>O1CCCC1>[NH2:14][C:19]1[N:24]=[C:23]([CH2:25][C:28]([O:30][CH2:5][CH3:6])=[O:29])[CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 8058HexaneHCID 112305162-[N,N-bis(trimethylsilyl)amino]-6-methylpyridineHCID 178418339Butyllithium

Product 1

HCID 13060163Ethyl (6-aminopyridin-2-yl)acetateYield 42.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 15% n-hexane solution (338.6 g.) of n-butyllithium was dropwise added to a solution of 6-[N,N-bis(trimethylsilyl)amino]-2-methylpyridine (100 g.) in anhydrous tetrahydrofuran (300 ml.) at -20° to -30° C. over one hour and the solution was stirred at 20° to 23° C. for one hour. The resultant solution was added in small portions to crushed dry ice (1 kg.) under stirring, and stirred till a room temperature. After removing tetrahydrofuran from the solution under reduced pressure, absolute ethanol (1 l) was added to the residue. 30% Ethanol solution (660 ml.) of hydrochloric acid was dropwise added to the solution at -5° to -10° C., and further hydrogen chloride gas was bubbled at 0° to 5° C. for 30 minutes and then the solution was stirred at 10° C. overnight. After removing ethanol from the resultant solution, the residue was dissolved in water, and washed with ethyl acetate 3 times. The solution was adjusted to pH 7 to 8 with sodium bicarbonate and extracted with ethyl acetate. The ethyl acetate extract was washed with a saturated aqueous solution of sodium chloride, dried and concentrated under reduced pressure to give the crude product (54 g.) The product was purified by column chromatography on silica gel (1 kg.) with an eluent (ethyl acetate+benzene) to give ethyl 2-(6-aminopyridin-2-yl)acetate (30.2 g.), mp 66° to 68° C.

Workup

  1. stirringunder stirring
  2. stirringstirred till a room temperature
  3. customAfter removing tetrahydrofuran from the solution under reduced pressure, absolute ethanol (1 l)
  4. additionwas added to the residue
  5. addition30% Ethanol solution (660 ml.) of hydrochloric acid was dropwise added to the solution at -5° to -10° C.
  6. customfurther hydrogen chloride gas was bubbled at 0° to 5° C. for 30 minutes
  7. stirringthe solution was stirred at 10° C. overnight
  8. customAfter removing ethanol from the resultant solution
  9. dissolutionthe residue was dissolved in water
  10. washwashed with ethyl acetate 3 times
  11. extractionextracted with ethyl acetate
  12. extractionThe ethyl acetate extract
  13. washwas washed with a saturated aqueous solution of sodium chloride
  14. customdried
  15. concentrationconcentrated under reduced pressure
  16. customto give the crude product (54 g.) The product
  17. customwas purified by column chromatography on silica gel (1 kg.) with an eluent (ethyl acetate+benzene)

Sources & evidence

ORD record
ord-cc283694328c43d9b33d0d036f45d1a5
Source dataset
uspto-grants-1986_06
Patent number
US04596869

Reaction notes

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