Ethanol → Ethyl 7-fluoroimidazo[1,2-a]pyridine-3-carboxylate

HRID 79248Notes

Reaction equation

HRID 79248 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=1.C(O)C.Cl[CH:13]([CH:19]=O)[C:14]([O:16][CH2:17][CH3:18])=[O:15].C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][N:5]2[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:19][N:8]=[C:4]2[CH:3]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 118030Ethyl (chloroformyl)acetateHCID 516892Sodium BicarbonateHCID 183278082-Amino-4-fluoropyridine

Product 1

HCID 67259301Ethyl 7-fluoroimidazo[1,2-a]pyridine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
60 °C

Procedure

4-Fluoropyridin-2-amine (10.0 g, 48.0 mmol) was mixed with ethanol (40 mL) in a reaction flask, under an atmosphere of dry nitrogen. A solution of ethyl 2-chloro-3-oxopropanoate (5% in benzene, 178 mL, Commercial solution from Toronto Research Chemicals Inc.) was added. The mixture was heated to 60° C. under nitrogen for 4 hours. After allowing the mixture to cool the solvent was removed under vacuum to give a brown solid. The solid was mixed with ethyl acetate (300 mL) and sodium bicarbonate solution (75 mL) and stirred to dissolve. The phases were separated and the bicarbonate solution was extracted further with ethyl acetate (75 mL). The combined ethyl acetate extracts were dried over sodium sulfate, filtered and concentrated under vacuum to give a solid. The crude material was dissolved in ethyl acetate and passed through a short column of silica, eluting with ethyl acetate. Fractions containing the product were concentrated to give ethyl 7-fluoroimidazo[1,2-a]pyridine-3-carboxylate as a white solid (13 g).

Workup

  1. temperatureto cool the solvent
  2. customwas removed under vacuum
  3. customto give a brown solid
  4. dissolutionto dissolve
  5. customThe phases were separated
  6. extractionthe bicarbonate solution was extracted further with ethyl acetate (75 mL)
  7. dry with materialThe combined ethyl acetate extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customto give a solid
  11. washeluting with ethyl acetate
  12. additionFractions containing the product
  13. concentrationwere concentrated

Sources & evidence

ORD record
ord-320df5308af348aba88469808923be3c
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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