Ethyl 4,4,4-trifluoroacetoacetate → HCID 178516597, compound

HRID 1747502Notes

Reaction equation

HRID 1747502 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3](=[O:10])[CH2:4][C:5]([O:7]CC)=O.[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([N:20]2[CH2:25][CH2:24][CH:23]([C:26]3[CH:30]=[C:29]([NH2:31])[NH:28][N:27]=3)[CH2:22][CH2:21]2)=[N:18][CH:19]=1.C(=O)(O)[O-].[Na+]>C(O)(=O)C>[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([N:20]2[CH2:21][CH2:22][CH:23]([C:26]3[C:30]4[C:3]([OH:10])([C:2]([F:1])([F:11])[F:12])[CH2:4][C:5](=[O:7])[NH:31][C:29]=4[NH:28][N:27]=3)[CH2:24][CH2:25]2)=[N:18][CH:19]=1

Participants

5

Reactant 3

HCID 67793Ethyl 4,4,4-trifluoroacetoacetateHCID 516892Sodium BicarbonateHCID 178507306HCID 178507306, compound

Product 1

HCID 178516597HCID 178516597, compoundYield 39.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

Ethyl trifluoroacetoacetate (1.28 g, 6.97 mmol) was added to a solution of 3-[1-(5-chloropyridin-2-yl)piperidin-4-yl]-1H-pyrazol-5-amine (0.484 g, 1.74 mmol) produced in Reference Example 20 in acetic acid (8 mL), and the mixture was stirred at 60° C. for 1.5 hours. A saturated sodium bicarbonate aqueous solution was added to the reaction solution, followed by extraction with ethyl acetate twice. 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=100/0-95/5 (gradient)] and further purified by silica gel column chromatography [elute: hexane/ethyl acetate=20/80-0/100 (gradient)] to obtain the title compound (0.283 g, yield: 39%).

Workup

  1. extractionfollowed by extraction with ethyl acetate twice
  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=100/0-95/5 (gradient)]
  6. customfurther purified by silica gel column chromatography [elute: hexane/ethyl acetate=20/80-0/100 (gradient)]

Sources & evidence

ORD record
ord-f64b1a3ea22744bf9187e2ccc7b97b6c
Source dataset
uspto-grants-2015_10
Patent number
US09150575B2

Reaction notes

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