Pyridine → Pentanoic acid {3-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-amide

HRID 1958656Notes

Reaction equation

HRID 1958656 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:21]([F:24])([F:23])[F:22])[O:13][N:12]=[C:11]([C:14]3[CH:15]=[C:16]([NH2:20])[CH:17]=[CH:18][CH:19]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.N1C=CC=CC=1.[C:31](Cl)(=[O:36])[CH2:32][CH2:33][CH2:34][CH3:35].C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:21]([F:22])([F:24])[F:23])[O:13][N:12]=[C:11]([C:14]3[CH:15]=[C:16]([NH:20][C:31](=[O:36])[CH2:32][CH2:33][CH2:34][CH3:35])[CH:17]=[CH:18][CH:19]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 61186Valeryl chlorideHCID 516892Sodium BicarbonateHCID 593556813-(5-(3,5-Dichlorophenyl)-4,5-dihydro-5-trifluoromethyl-3-isoxazolyl)aniline

Product 1

HCID 59549498Pentanoic acid {3-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-amideYield 89%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenylamine (0.150 mg, 0.40 mmol) (Example I3) in tetrahydrofuran (4 ml) was added pyridine (0.085 ml, 1.06 mmol). Pentanoyl chloride (0.063 ml, 0.53 mmol) was added under vigorous stirring at ambient temperature. The reaction mixture was stirred for 3 hours at ambient temperature. Aqueous sodium hydrogen carbonate (saturated) and ethyl acetate was added and the phases were separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic extracts were dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 2:1) to give Compound No. A6 of Table A (0.165 g, 89% yield). 1H-NMR (400 MHz, CDCl3): 8.00 (s, 1H), 7.70 (s, 1H), 7.53 (d, 1H), 7.49 (s, 2H), 7.42 (m, 2H), 7.35 (m, 1H), 4.09 (d, 1H), 3.72 (d, 1H), 2.40 (t, 2H), 1.70 (m, 2H), 1.40 (m, 2H), 0.94 (t, 3H).

Workup

  1. stirringThe reaction mixture was stirred for 3 hours at ambient temperature
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted twice with ethyl acetate
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 2:1)
  7. customto give Compound No

Sources & evidence

ORD record
ord-d28f820e057843af8d6c51f797bc50b9
Source dataset
uspto-grants-2013_04
Patent number
US08410145B2

Reaction notes

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