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

HRID 2401631Notes

Reaction equation

HRID 2401631 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 3A 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-4c075378579e4a8f8d3766a30c6933c0
Source dataset
uspto-grants-2014_08
Patent number
US08796305B2

Reaction notes

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