Tetrahydrofuran → HCID 67188224, compound

HRID 885807Notes

Reaction equation

HRID 885807 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:22]([F:25])([F:24])[F:23])[O:13][N:12]=[C:11]([C:14]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[C:26]1([Mg]Br)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[O:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:22]([F:23])([F:25])[F:24])[O:13][N:12]=[C:11]([C:14]3[CH:15]=[CH:16][C:17]([CH:18]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[NH:19][C:38]([CH:37]4[CH2:35][CH2:36]4)=[O:34])=[CH:20][CH:21]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 67190564HCID 67190564, compoundHCID 178418255HCID 178418255, compound

Product 1

HCID 67188224HCID 67188224, compound

Procedure

In a solution of 0.80 g of 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]benzonitrile in 10 mL of tetrahydrofuran under nitrogen atmosphere, 1.0 mL of 32% tetrahydrofuran solution of phenyl magnesium bromide was added dropwise with stirring at room temperature, after the completion of the addition dropwise, it was continued to stir at room temperature further for 3.5 hours. After the completion of the reaction, the solvent was distilled off under reduced pressure, the residue was dissolved in 10 mL of methanol, 0.075 g of sodium boron hydride was added, and stirred at room temperature for 2 hours. The reaction mixture was diluted with 20 mL of ethyl acetate, washed with water (10 mL×2), and the organic phase was dehydrated with and dried over saturated sodium chloride aqueous solution and anhydrous magnesium sulfate in that order, and the solvent was distilled off under reduced pressure. The residue was dissolved in 20 mL of chloroform, and under cooling with ice and with stirring, 0.20 g of triethyl amine and 0.21 g of cyclopropanecarbonyl=chloride were added dropwise, after the completion of the addition dropwise, it was continued to stir at room temperature further for 1 hour. After the completion of the reaction, the reaction mixture was washed with water (10 mL×1), and the organic phase was dehydrated with and dried over saturated sodium chloride aqueous solution and anhydrous magnesium sulfate in that order, and the solvent was distilled off under reduced pressure. The residue was purified with medium pressure preparative liquid chromatography (medium pressure collection apparatus: YFLC-Wprep manufactured by Yamazen Corporation) that was eluted with ethyl acetate-hexane (gradient of 1:9 to 1:2) to obtain 0.16 g of the aimed products as colorless resinous substance.

Workup

  1. additionafter the completion of the addition dropwise
  2. stirringto stir at room temperature further for 3.5 hours
  3. customAfter the completion of the reaction
  4. distillationthe solvent was distilled off under reduced pressure
  5. dissolutionthe residue was dissolved in 10 mL of methanol
  6. addition0.075 g of sodium boron hydride was added
  7. stirringstirred at room temperature for 2 hours
  8. additionThe reaction mixture was diluted with 20 mL of ethyl acetate
  9. washwashed with water (10 mL×2)
  10. dry with materialdried over saturated sodium chloride aqueous solution and anhydrous magnesium sulfate in that order
  11. distillationthe solvent was distilled off under reduced pressure
  12. dissolutionThe residue was dissolved in 20 mL of chloroform
  13. temperatureunder cooling with ice
  14. stirringwith stirring
  15. addition0.20 g of triethyl amine and 0.21 g of cyclopropanecarbonyl=chloride were added dropwise
  16. additionafter the completion of the addition dropwise
  17. stirringto stir at room temperature further for 1 hour
  18. customAfter the completion of the reaction
  19. washthe reaction mixture was washed with water (10 mL×1)
  20. dry with materialdried over saturated sodium chloride aqueous solution and anhydrous magnesium sulfate in that order
  21. distillationthe solvent was distilled off under reduced pressure
  22. customThe residue was purified with medium pressure preparative liquid chromatography (medium pressure collection apparatus: YFLC-Wprep manufactured by Yamazen Corporation) that
  23. washwas eluted with ethyl acetate-hexane (gradient of 1:9 to 1:2)

Sources & evidence

ORD record
ord-e67549dda3594742bc1fdbec66f5375d
Source dataset
uspto-grants-2012_08
Patent number
US08242283B2

Reaction notes

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