Reaction #470406

ord-c35ce055db994dbca3abd04216ff14cc

Reaction equation

Oc1ccccn1
2-hydroxypyridine
O=C([O-])[O-].[K+].[K+]
K2CO3
O=C(O)c1ccc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)c2ccccc12
4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylic acid
O=C(Cl)C(=O)Cl
oxalyl chloride
O=C(Oc1ccccn1)c1ccc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)c2ccccc12
title product
Yield 46.0%
O=C(Oc1ccccn1)c1ccc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)c2ccccc12
2-pyridinyl 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylate
Yield 46.0%

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Otherprepared
  2. 2
    Otherat room temperature
  3. 3
    Concentrationconcentrated under vacuum
  4. 4
    workup.DISSOLUTIONThe residue was dissolved in dichloromethane (10 mL)
  5. 5
    OtherThe resulting reaction mixture
  6. 6
    workup.STIRRINGwas stirred at room temperature overnight
  7. 7
    FiltrationThe reaction mixture was filtered through a short pad of Celite® diatomaceous filter aid
  8. 8
    Washthe pad was rinsed with dichloromethane
  9. 9
    ConcentrationThe combined filtrate was concentrated
  10. 10
    Otherthe residue was purified by column chromatography on silica gel

Procedure

To a stirred suspension of 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylic acid (prepared according to the procedure described in WO 2007/079162, 1.50 g, 3.30 mmol) in dichloromethane (15 mL) at room temperature was added oxalyl chloride (0.58 mL, 6.60 mmol) followed by one drop of N,N-dimethylformamide. The reaction mixture was stirred at room temperature for 2 h and then concentrated under vacuum. The residue was dissolved in dichloromethane (10 mL) and added to a stirred suspension of 2-hydroxypyridine (0.38 g, 3.96 mmol) and K2CO3 (1.37 g, 9.90 mmol) in dichloromethane (15 mL) at room temperature. The resulting reaction mixture was stirred at room temperature overnight. The reaction mixture was filtered through a short pad of Celite® diatomaceous filter aid, and the pad was rinsed with dichloromethane. The combined filtrate was concentrated and the residue was purified by column chromatography on silica gel using hexane/EtOAc as eluent to provide the title product as a yellow solid (0.80 g, 46% yield).

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08367584B2uspto-grants-2013_02