Ethyl 2-chloroacetoacetate → Ethyl 8-(benzyloxy)-2-methylimidazo[1,2-A]pyridine-3-carboxylate

HRID 2275780Notes

Reaction equation

HRID 2275780 reaction equation
[NH2:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.Cl[CH:17]([C:23]([CH3:25])=O)[C:18]([O:20][CH2:21][CH3:22])=[O:19]>C(O)C>[CH2:9]([O:8][C:7]1[C:2]2[N:3]([C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:23]([CH3:25])[N:1]=2)[CH:4]=[CH:5][CH:6]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

4

Reactant 2

HCID 11858Ethyl 2-chloroacetoacetateHCID 903342-Amino-3-benzyloxypyridine

Product 1

HCID 44382335Ethyl 8-(benzyloxy)-2-methylimidazo[1,2-A]pyridine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

25 g of 2-amino-3-benzyloxypyridine (124.8 mmol, 1 equivalent) were dissolved in 781 ml of ethanol, and 102.7 g of ethyl 2-chloroacetoacetate (624.2 mmol, 5 equivalents) and 15 g of 4 Å molecular sieve were added. The mixture was heated at reflux for 2 d (bath temperature 100° C.). The mixture was then concentrated and excess ethyl 2-chloroacetoacetate was distilled off on a rotary evaporator with dry ice-cooling. The residue was purified by silica gel chromatography (mobile phase cyclohexane:ethyl acetate 9:1, 4:1). This gave 20.81 g of the title compound (54% of theory).

Workup

  1. temperatureThe mixture was heated
  2. concentrationThe mixture was then concentrated
  3. distillationexcess ethyl 2-chloroacetoacetate was distilled off on a rotary evaporator with dry ice-
  4. temperaturecooling
  5. customThe residue was purified by silica gel chromatography (mobile phase cyclohexane:ethyl acetate 9:1, 4:1)

Sources & evidence

ORD record
ord-3201e1dab2c7448dae1b0112daf3a1b6
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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