Potassium Carbonate → HCID 23642252, compound

HRID 598756Notes

Reaction equation

HRID 598756 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:12][C:11]([C:17]3[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([Cl:24])[CH:18]=3)([C:13]([F:16])([F:15])[F:14])[O:10][N:9]=2)=[CH:4][CH:3]=1.C([Li])CCC.[CH3:30][S:31](=[O:35])(SC)=[O:32].[OH-].[Na+].ClC1C=C(C=CC=1)C(OO)=O.S(=O)(O)[O-].[Na+].C(=O)([O-])[O-].[K+].[K+]>O1CCCC1>[Cl:24][C:19]1[CH:18]=[C:17]([C:11]2([C:13]([F:16])([F:15])[F:14])[O:10][N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([S:31]([CH3:30])(=[O:35])=[O:32])=[CH:3][CH:4]=3)[CH2:12]2)[CH:22]=[C:21]([Cl:23])[CH:20]=1

Participants

9

Reactant 7

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 18064S-Methyl methanethiosulfonateHCID 70297m-Chloroperbenzoic acid2×HCID 23665763Sodium BisulfiteHCID 86626432HCID 86626432, compoundHCID 178418339Butyllithium

Product 1

HCID 23642252HCID 23642252, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(4-bromophenyl)-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazole (i.e. the product of Step A) (4.39 mg, 1.00 mmol) in tetrahydrofuran (10 mL) cooled below −75° C. was added a solution of n-butyllithium (2.5 M solution in hexanes) dropwise over three minutes, while maintaining the temperature at or below −72° C. Within one minute, S-methyl methanesulfonothioate (0.11=L, 1.2 mmol) was added dropwise. The reaction mixture was allowed to stir and warm slowly to ambient temperature, and then it was poured into 1 N aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate; and concentrated. The residue was subjected to chromatography on silica gel eluted with 10% ethyl acetate in hexanes. The isolated material was redissolved in dichloromethane (5 mL), treated with 3-chloroperoxybenzoic acid (˜77%, 0.39 g, 1.7 mmol) and allowed to stir at ambient temperature for 64 h. Additional 3-chloroperoxybenzoic acid (˜77%, 0.27 g, 1.2 mmol) was added, and the mixture was stirred for 4 h. To this mixture was added saturated aqueous sodium bisulfite solution, and then solid potassium carbonate was added carefully until gas evolution ceased. The phases were separated, and the organic phase was washed with 1 N aqueous sodium hydroxide solution and with saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated. The residue was triturated with diethyl ether and hexanes to obtain a solid which was collected on a glass frit. The solid was washed with a mixture of diether and hexanes, and dried to afford the title product (0.12 g), a compound of the present invention.

Workup

  1. temperaturewhile maintaining the temperature at or below −72° C
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic phase was washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. concentrationand concentrated
  6. washeluted with 10% ethyl acetate in hexanes
  7. dissolutionThe isolated material was redissolved in dichloromethane (5 mL)
  8. stirringto stir at ambient temperature for 64 h
  9. stirringthe mixture was stirred for 4 h
  10. customThe phases were separated
  11. washthe organic phase was washed with 1 N aqueous sodium hydroxide solution and with saturated aqueous sodium chloride solution
  12. dry with materialdried over magnesium sulfate
  13. concentrationconcentrated
  14. customThe residue was triturated with diethyl ether and hexanes
  15. customto obtain a solid which
  16. customwas collected on a glass frit
  17. washThe solid was washed with a mixture of diether and hexanes
  18. customdried

Sources & evidence

ORD record
ord-0eeaf260244a4a1ba81ee5665a593449
Source dataset
uspto-grants-2011_03
Patent number
US07897630B2

Reaction notes

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