Methanol → Methyl 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoate

HRID 467932Notes

Reaction equation

HRID 467932 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:24]([F:27])([F:26])[F:25])[O:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[C:16]([CH3:23])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.S(Cl)(Cl)=O.[CH3:32]O>C1(C)C=CC=CC=1.CN(C)C=O>[CH3:32][O:19][C:18](=[O:20])[C:17]1[CH:21]=[CH:22][C:14]([C:11]2[CH2:10][C:9]([C:4]3[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=3)([C:24]([F:25])([F:27])[F:26])[O:13][N:12]=2)=[CH:15][C:16]=1[CH3:23]

Participants

6

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 231598114-(5-(3,5-Dichlorophenyl)-5-(tri fluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid

Product 1

HCID 59563501Methyl 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid (Example I5) (10 g) in toluene (150 ml) and dimethylformamide (0.1 ml) at ambient temperature was added dropwise thionyl chloride (3.5 ml). The reaction mixture was stirred at 50° C. for 2 hours. The solution was then cooled to 0° C. and methanol (2 ml) added slowly. The reaction mixture was stirred at ambient temperature for 1 hour. The reaction mixture was concentrated and aqueous sodium hydrogen carbonate (saturated) (50 ml) added to the residue. The mixture was extracted with ethyl acetate (3×100 ml). The combined organic extracts were dried over sodium sulfate and concentrated to afford 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid methyl ester as a yellow solid (11.5 g). 1H-NMR (CDCl3, 400 MHz): 7.95 (d, 1H), 7.55 (m, 4H), 7.45 (s, 1H), 4.10 (d, 1H), 3.90 (s, 3H), 3.70 (d, 1H), 2.60 (s, 3H) ppm.

Workup

  1. customat ambient temperature
  2. temperatureThe solution was then cooled to 0° C.
  3. stirringThe reaction mixture was stirred at ambient temperature for 1 hour
  4. concentrationThe reaction mixture was concentrated
  5. additionaqueous sodium hydrogen carbonate (saturated) (50 ml) added to the residue
  6. extractionThe mixture was extracted with ethyl acetate (3×100 ml)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-d3de05240e99441e92f785444499927a
Source dataset
uspto-grants-2014_01
Patent number
US08623896B2

Reaction notes

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