Ethyl 2-chloroacetoacetate → HCID 86717873, compound

HRID 1844125Notes

Reaction equation

HRID 1844125 reaction equation
[NH2:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([F:9])=[CH:4][N:3]=1.Cl[CH:11]([C:17]([CH3:19])=O)[C:12]([O:14][CH2:15][CH3:16])=[O:13]>C(O)C>[F:9][C:5]1[CH:6]=[C:7]([OH:8])[C:2]2[N:3]([C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:17]([CH3:19])[N:1]=2)[CH:4]=1

Participants

4

Reactant 2

HCID 11858Ethyl 2-chloroacetoacetateHCID 214366912-Amino-5-fluoropyridin-3-ol

Product 1

HCID 86717873HCID 86717873, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

3.2 g of 2-amino-5-fluoropyridin-3-ol (Example 11A; 25 mmol, 1 equivalent) were initially charged in 155 ml of ethanol, 1.5 g of powdered molecular sieve 3 Å and 20.6 g of ethyl 2-chloroacetoacetate (125 mmol, 5 equivalents) were added and the mixture was heated at reflux overnight. The reaction solution was concentrated and chromatographed (Biotage Isolera Four; SNAP Cartridge KP-Sil 50 g; cyclohexane/ethyl acetate gradient; then dichloromethane/methanol gradient). The crude product was partly dissolved in a little methanol, and tert-butyl methyl ether was added. The solid obtained was filtered off and rinsed with tert-butyl methyl ether. This gave 570 mg (10% of theory) of the title compound.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux overnight
  3. concentrationThe reaction solution was concentrated
  4. customchromatographed (Biotage Isolera Four
  5. dissolutionThe crude product was partly dissolved in a little methanol, and tert-butyl methyl ether
  6. additionwas added
  7. customThe solid obtained
  8. filtrationwas filtered off
  9. washrinsed with tert-butyl methyl ether

Sources & evidence

ORD record
ord-8bb53776571c41f5be6c85a090104819
Source dataset
uspto-grants-2015_02
Patent number
US08946215B2

Reaction notes

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