Ethyl 2-chloroacetoacetate → HCID 86717873, compound

HRID 2275761Notes

Reaction equation

HRID 2275761 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 8A; 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 boiled 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 was filtered off and washed with tert-butyl methyl ether. This gave 570 mg (10% of theory) of the title compound.

Workup

  1. temperatureat reflux overnight
  2. concentrationThe reaction solution was concentrated
  3. customchromatographed (Biotage Isolera Four
  4. dissolutionThe crude product was partly dissolved in a little methanol, and tert-butyl methyl ether
  5. additionwas added
  6. filtrationThe solid was filtered off
  7. washwashed with tert-butyl methyl ether

Sources & evidence

ORD record
ord-7d7ea9edbf034c86bfecf1fc8400b0f1
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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