Methyl chloroformate → Methyl n-[4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-methylbenzoyl]-n-(2-tetrahydrofuranyl)carbamate

HRID 1187974Notes

Reaction equation

HRID 1187974 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([C:11]2([C:31]([F:34])([F:33])[F:32])[O:15][N:14]=[C:13]([C:16]3[CH:29]=[CH:28][C:19]([C:20]([NH:22][CH:23]4[CH2:27][CH2:26][CH2:25][O:24]4)=[O:21])=[C:18]([CH3:30])[CH:17]=3)[CH2:12]2)[CH:7]=[C:8]([Cl:10])[CH:9]=1.Cl[C:36]([O:38][CH3:39])=[O:37]>O1CCCC1.O>[Cl:3][C:4]1[CH:5]=[C:6]([C:11]2([C:31]([F:33])([F:32])[F:34])[O:15][N:14]=[C:13]([C:16]3[CH:29]=[CH:28][C:19]([C:20]([N:22]([CH:23]4[CH2:27][CH2:26][CH2:25][O:24]4)[C:36](=[O:37])[O:38][CH3:39])=[O:21])=[C:18]([CH3:30])[CH:17]=3)[CH2:12]2)[CH:7]=[C:8]([Cl:10])[CH:9]=1

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 24758Sodium hydrideHCID 252170264-[5-(3,5-Dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methyl-N-(2-tetrahydrofuranyl) benzoic acid amide

Product 1

HCID 67165269Methyl n-[4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-methylbenzoyl]-n-(2-tetrahydrofuranyl)carbamateYield 23.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

In a suspension of 0.07 g of 55% oily sodium hydride in 10 mL of tetrahydrofuran, a solution of 0.49 g of 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-methyl-N-(2-tetrahydrofuranyl)benzoic acid amide in 5 mL of tetrahydrofuran was added dropwise under cooling with ice and with stirring. After the completion of the addition dropwise, it was stirred at room temperature for 10 minutes. Then, 0.15 g of methyl chloroformate was added, and continued to stir at the same temperature further for 15 hours. After the completion of the reaction, the reaction was poured in 10 mL of water, extracted with ethyl acetate (20 mL×2), the organic phase was dehydrated with and dried over saturated sodium chloride aqueous solution and then anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that was eluated with ethyl acetate-hexane (2:3) to obtain 0.13 g of the aimed product as colorless resinous substance.

Workup

  1. temperatureunder cooling with ice
  2. additionAfter the completion of the addition dropwise
  3. stirringit was stirred at room temperature for 10 minutes
  4. stirringto stir at the same temperature further for 15 hours
  5. customAfter the completion of the reaction
  6. extractionextracted with ethyl acetate (20 mL×2)
  7. dry with materialdried over saturated sodium chloride aqueous solution
  8. distillationanhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure
  9. customThe residue was purified with silica gel column chromatography that

Sources & evidence

ORD record
ord-5637503ffbc54f7b807beaf24a1952b6
Source dataset
uspto-grants-2014_03
Patent number
US08673951B2

Reaction notes

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