Ethyl 2-chloroacetoacetate → HCID 86717873, compound

HRID 1624066Notes

Reaction equation

HRID 1624066 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-2613f06de9484f7aa3b11be2acde3bf3
Source dataset
uspto-grants-2014_07
Patent number
US08778964B2

Reaction notes

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