Ethyl 2-chloroacetoacetate → Ethyl 6-chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate

HRID 2275767Notes

Reaction equation

HRID 2275767 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:9][CH2:10][C:11]2[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]=2[F:18])[C:5]([NH2:8])=[N:6][CH:7]=1.Cl[CH:20]([C:26]([CH3:28])=O)[C:21]([O:23][CH2:24][CH3:25])=[O:22]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([O:9][CH2:10][C:11]2[C:12]([F:18])=[CH:13][CH:14]=[CH:15][C:16]=2[F:17])[C:5]2[N:6]([C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:26]([CH3:28])[N:8]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 11858Ethyl 2-chloroacetoacetateHCID 867178775-Chloro-3-[(2,6-difluorobenzyl)oxy]pyridine-2-amine

Product 1

HCID 86717878Ethyl 6-chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

40 g of 5-chloro-3-[(2,6-difluorobenzyl)oxy]pyridine-2-amine (Example 14A; 147.8 mmol; 1 equivalent) were initially charged in 800 ml of ethanol, 30 g of powdered molecular sieve 3 Å and 128 g of ethyl 2-chloroacetoacetate (739 mmol, 5 equivalents) were added and the mixture was heated at reflux overnight. The reaction mixture was concentrated and the residue was taken up in ethyl acetate and filtered. The ethyl acetate phase was washed with water, dried, filtered and concentrated. This gave 44 g (78% of theory) of the title compound.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux overnight
  3. concentrationThe reaction mixture was concentrated
  4. filtrationfiltered
  5. washThe ethyl acetate phase was washed with water
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-50eb6fe81dc449249f51073b1e2f59b6
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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