Ethyl (chloroformyl)acetate → 7-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyridine-3-carboxylic acid ethyl ester

HRID 269038Notes

Reaction equation

HRID 269038 reaction equation
[NH2:1][N:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)=[CH:4][C:3]1=S.[CH2:23]([O:25][C:26](=[O:31])[CH:27](Cl)[CH:28]=O)[CH3:24].C([O-])(O)=O.[Na+]>CCO>[CH2:23]([O:25][C:26]([C:27]1[CH:28]=[N:1][N:2]2[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5]([C:12]3[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=3)=[CH:4][C:3]=12)=[O:31])[CH3:24]

Participants

5

Reactant 3

HCID 118030Ethyl (chloroformyl)acetate4×HCID 516892Sodium BicarbonateHCID 866080141-amino-6-trifluoromethyl-4-(4-trifluoromethyl-phenyl)-1H-pyridine-2-thione

Product 1

HCID 866080137-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyridine-3-carboxylic acid ethyl esterYield 62%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 1-amino-6-trifluoromethyl-4-(4-trifluoromethyl-phenyl)-1H-pyridine-2-thione (example C.22 step 6) (3.14 g, 9.28 mmol) and 2-chloro-3-oxo-propionic acid ethyl ester (example C.22 reagent 1) (4.19 g, 27.85 mmol) in EtOH (45 mL) was refluxed for 20 h, the added again 2-chloro-3-oxo-propionic acid ethyl ester (example C.22 reagent 1) (2.20 g, 14.61 mmol) and refluxing was continued for another 18 h. Poured into sat. NaHCO3-sol., extracted with EtOAc, washed the organic layer with brine, dried over Na2SO4 and evaporated to leave a residue, which was purified by flash chromatography (600 g SiO2) with heptane/EtOAc 9:1, followed by trituration with heptane (ca. 50 mL) at −70° C. to give the title compound as a light yellow solid (2.30 g, 62%). MS (ISP) 403 [(M+H)+]; mp 130° C.

Workup

  1. customwas refluxed for 20 h
  2. temperaturerefluxing
  3. extraction, extracted with EtOAc
  4. washwashed the organic layer with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customto leave a residue, which
  8. customwas purified by flash chromatography (600 g SiO2) with heptane/EtOAc 9:1
  9. customfollowed by trituration with heptane (ca. 50 mL) at −70° C.

Sources & evidence

ORD record
ord-4fb587bbda184933a6a622864b98c8f1
Source dataset
uspto-grants-2008_11
Patent number
US07446113B2

Reaction notes

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