Hydrochloric Acid → 3-(5-(3,5-Dichlorophenyl)-4,5-dihydro-5-trifluoromethyl-3-isoxazolyl)aniline

HRID 1958653Notes

Reaction equation

HRID 1958653 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:23]([F:26])([F:25])[F:24])[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([N+:20]([O-])=O)[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[Sn](Cl)Cl.Cl>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:23]([F:25])([F:24])[F:26])[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

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 24479Stannous ChlorideHCID 593556103-(5-(3,5-Dichlorophenyl)-4,5-dihydro-5-trifluoromethyl-3-isoxazolyl)nitrobenzene

Product 1

HCID 593556813-(5-(3,5-Dichlorophenyl)-4,5-dihydro-5-trifluoromethyl-3-isoxazolyl)anilineYield 58.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-(3,5-dichloro-phenyl)-3-(3-nitro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole (15.0 g, 37 mmol) (Example I2) in isopropanol (120 ml) was added tin(II) chloride (25 g, 133 mmol). The mixture was cooled to 0° C. and aqueous hydrochloric acid (concentrated) (23 ml) was added slowly at 0° C. The reaction mixture was heated to 80° C. for 2 hours. Then ⅓ of the total volume of isopropanol was evaporated. Water (100 ml) was added to the mixture and aqueous sodium hydroxide (4N) was added to adjust the pH to 8-9. The aqueous phase was extracted three times with ethyl acetate (200 ml). The combined organic extracts were dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 1:1) to give 3-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenylamine (8.1 g, 58% yield). 1H-NMR (CDCl3, 400 MHz): 7.56 (m, 2H), 7.43 (m, 1H), 7.20 (t, 1H), 7.05 (m, 1H), 6.97 (m, 1H), 6.78 (m, 1H), 4.08 (d, 1H), 3.8 (s, 1H), 3.68 (d, 1H).

Workup

  1. temperatureThe reaction mixture was heated to 80° C. for 2 hours
  2. customThen ⅓ of the total volume of isopropanol was evaporated
  3. additionWater (100 ml) was added to the mixture and aqueous sodium hydroxide (4N)
  4. additionwas added
  5. extractionThe aqueous phase was extracted three times with ethyl acetate (200 ml)
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-9c405e637a944415ba74380c69dcb6c2
Source dataset
uspto-grants-2013_04
Patent number
US08410145B2

Reaction notes

Loading…