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

HRID 706530Notes

Reaction equation

HRID 706530 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+]>C1C=CC=CC=1.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

7

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 2

HCID 241BenzeneSolventHCID 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. Factions containing the desired 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. additionFactions containing the desired product
  13. concentrationwere concentrated

Sources & evidence

ORD record
ord-ae265b0166d2470ca74f5535f50eba39
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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