Ethyl 4,4,4-trifluoroacetoacetate → HCID 178516594, compound

HRID 1747500Notes

Reaction equation

HRID 1747500 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3](=[O:10])[CH2:4][C:5]([O:7]CC)=O.[C:13]1([N:19]2[CH2:24][CH2:23][CH:22]([C:25]3[CH:29]=[C:28]([NH2:30])[NH:27][N:26]=3)[CH2:21][CH2:20]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)(O)[O-].[Na+]>C(O)(=O)C>[OH:10][C:3]1([C:2]([F:1])([F:11])[F:12])[CH2:4][C:5](=[O:7])[NH:30][C:28]2[NH:27][N:26]=[C:25]([CH:22]3[CH2:21][CH2:20][N:19]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[CH2:24][CH2:23]3)[C:29]1=2

Participants

5

Reactant 3

HCID 67793Ethyl 4,4,4-trifluoroacetoacetateHCID 516892Sodium BicarbonateHCID 178507304HCID 178507304, compound

Product 1

HCID 178516594HCID 178516594, compoundYield 42.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

Ethyl trifluoroacetoacetate (1.50 g, 8.15 mmol) was added to a solution of 3-(1-phenylpiperidin-4-yl)-1H-pyrazol-5-amine (648 mg, 2.67 mmol) produced in Reference Example 3 in acetic acid (10 mL), and the mixture was stirred at 60° C. for 2 hours and 30 minutes. A saturated sodium bicarbonate aqueous solution was added to the reaction solution, followed by extraction with ethyl acetate. The obtained organic layer was washed with brine and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [NH-silica gel column, elute: ethyl acetate/methanol=100/0-96/4 (gradient)] and further purified by silica gel chromatography [elute: hexane/ethyl acetate=60/40-0/100 (gradient)] to obtain the title compound (430 mg, yield: 42%).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe obtained organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography [NH-silica gel column, elute: ethyl acetate/methanol=100/0-96/4 (gradient)]
  6. customfurther purified by silica gel chromatography [elute: hexane/ethyl acetate=60/40-0/100 (gradient)]

Sources & evidence

ORD record
ord-a2fd1afdc2574f7499ad6c03b5eb66e0
Source dataset
uspto-grants-2015_10
Patent number
US09150575B2

Reaction notes

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