Hydrochloric Acid → Methyl 3-(4,5-dihydroisoxazol-3-yl)-4-methylsulfonyl-2-methylbenzoate

HRID 1857313Notes

Reaction equation

HRID 1857313 reaction equation
[OH:1][N:2]=[CH:3][C:4]1[C:5]([CH3:18])=[C:6]([CH:11]=[CH:12][C:13]=1[S:14]([CH3:17])(=[O:16])=[O:15])[C:7]([O:9][CH3:10])=[O:8].C=C.[CH2:21](N(CC)CC)[CH3:22].Cl>[Cl].C(Cl)(Cl)Cl.CCOCC.O>[O:1]1[CH2:22][CH2:21][C:3]([C:4]2[C:5]([CH3:18])=[C:6]([CH:11]=[CH:12][C:13]=2[S:14]([CH3:17])(=[O:15])=[O:16])[C:7]([O:9][CH3:10])=[O:8])=[N:2]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6325Ethylene2×HCID 8471TriethylamineHCID 86756010Methyl 3-hydroxyiminomethyl-4-methylsulfonyl-2-methylbenzoate

Product 1

HCID 22129428Methyl 3-(4,5-dihydroisoxazol-3-yl)-4-methylsulfonyl-2-methylbenzoate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 178478478HCID 178478478, compoundSolvent

Procedure

6.00 g of crude methyl 3-hydroxyiminomethyl-4-methylsulfonyl-2-methylbenzoate was dissolved in 100 ml of chloroform Chlorine was blown into the resulting solution, with stirring, for 35 minutes at -3~3° C. The solution was further stirred for 30 minutes at 0° C. Nitrogen gas was blown into the reaction solution to remove excessive chlorine. Further chloroform was distilled out under reduced pressure to give viscous oil. The obtained oil was dissolved in 90 ml of ether, and ethylene was blown in, with stirring, for 5 minutes at -10° C. Then 7 ml of triethylamine and 7 ml of ether were added dropwise at -10° C. Further ethylene was blown in for 20 minutes. The resulting reaction mixture was transferred to a 200 ml, stainless-steel autoclave, which was cooled beforehand, and stirred for 3.5 hours at 60~70° C. The reaction solution was cooled down, poured into water, acidified with hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with water, then with a saturated sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was distilled out under reduced pressure. The obtained crude product was purified by column chromatography on silica gel with n-hexane/ethyl acetate=2/1 to give 3.20 g of the title compound as white crystals. m.p. 104~106.5° C.

Workup

  1. stirringThe solution was further stirred for 30 minutes at 0° C
  2. customto remove excessive chlorine
  3. distillationFurther chloroform was distilled out under reduced pressure
  4. customto give viscous oil
  5. stirringwith stirring, for 5 minutes at -10° C
  6. customwas blown in for 20 minutes
  7. customThe resulting reaction mixture
  8. stirringstirred for 3.5 hours at 60~70° C
  9. temperatureThe reaction solution was cooled down
  10. extractionextracted with ethyl acetate
  11. washThe organic layer was washed with water
  12. dry with materialwith a saturated sodium chloride solution, and dried over anhydrous magnesium sulfate
  13. distillationThe solvent was distilled out under reduced pressure
  14. customThe obtained crude product
  15. customwas purified by column chromatography on silica gel with n-hexane/ethyl acetate=2/1

Sources & evidence

ORD record
ord-84e5069f59fc416c9beaffd9c20c52b4
Source dataset
uspto-grants-2000_11
Patent number
US06147031

Reaction notes

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