Ethyl 4,4,4-trifluoroacetoacetate → HCID 178516595, compound

HRID 1747501Notes

Reaction equation

HRID 1747501 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3](=[O:10])[CH2:4][C:5]([O:7]CC)=O.[F:13][C:14]([F:34])([F:33])[C:15]1[CH:16]=[CH:17][C:18]([N:21]2[CH2:26][CH2:25][CH:24]([C:27]3[CH:31]=[C:30]([NH2:32])[NH:29][N:28]=3)[CH2:23][CH2:22]2)=[N:19][CH:20]=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:32][C:30]2[NH:29][N:28]=[C:27]([CH:24]3[CH2:25][CH2:26][N:21]([C:18]4[CH:17]=[CH:16][C:15]([C:14]([F:13])([F:34])[F:33])=[CH:20][N:19]=4)[CH2:22][CH2:23]3)[C:31]1=2

Participants

5

Reactant 3

HCID 67793Ethyl 4,4,4-trifluoroacetoacetateHCID 516892Sodium BicarbonateHCID 178507305HCID 178507305, compound

Product 1

HCID 178516595HCID 178516595, compoundYield 48%

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-[5-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}-1H-pyrazol-5-amine (880 mg, 2.83 mmol) produced in Reference Example 10 in acetic acid (10 mL), and the mixture was stirred at 60° C. for 2 hours. A saturated sodium bicarbonate aqueous solution was added to the reaction solution, followed by extraction with ethyl acetate three times. 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 column chromatography [elute: hexane/ethyl acetate=60/40-0/100 (gradient)] to obtain the title compound (610 mg, yield: 48%).

Workup

  1. extractionfollowed by extraction with ethyl acetate three times
  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 column chromatography [elute: hexane/ethyl acetate=60/40-0/100 (gradient)]

Sources & evidence

ORD record
ord-50c842f5f2e14108a3848a44a5d76bd3
Source dataset
uspto-grants-2015_10
Patent number
US09150575B2

Reaction notes

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