Pyridine → N-Carbamoylmethyl-4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-methyl benzoic acid amide

HRID 452520Notes

Reaction equation

HRID 452520 reaction equation
Cl.[NH2:2][CH2:3][C:4]([NH2:6])=[O:5].N1C=CC=CC=1.[Cl:13][C:14]1[CH:15]=[C:16]([C:21]2([C:36]([F:39])([F:38])[F:37])[O:25][N:24]=[C:23]([C:26]3[CH:34]=[CH:33][C:29]([C:30](Cl)=[O:31])=[C:28]([CH3:35])[CH:27]=3)[CH2:22]2)[CH:17]=[C:18]([Cl:20])[CH:19]=1.C(N(CC)CC)C>ClCCl>[C:4]([CH2:3][NH:2][C:30](=[O:31])[C:29]1[CH:33]=[CH:34][C:26]([C:23]2[CH2:22][C:21]([C:16]3[CH:17]=[C:18]([Cl:20])[CH:19]=[C:14]([Cl:13])[CH:15]=3)([C:36]([F:39])([F:38])[F:37])[O:25][N:24]=2)=[CH:27][C:28]=1[CH3:35])(=[O:5])[NH2:6]

Participants

6

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 2723639Glycinamide hydrochlorideHCID 866114794-(5-(3,5-Dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl)-2-methylbenzoyl chloride

Product 1

HCID 66784362N-Carbamoylmethyl-4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-methyl benzoic acid amideYield 87.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

In a solution of 0.37 g of glycine amide hydrochloride and 0.71 g of pyridine in 20 ml of dichloromethane, a solution of 1.31 g of 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methylbenzoyl chloride synthesized in Step 3 of Synthetic Example 29 in 10 ml of dichloromethane was added dropwise with stirring under ice cooling, after the completion of the addition, stirred at room temperature for 3 hours, then 3.00 g of triethyl amine was added in the reaction mixture, and continued to stir at the same temperature further for 30 minutes. After the completion of the reaction, the solvent was distilled off under reduced pressure, 50 ml of ethyl acetate and 50 ml of water were added in the residue, and the organic phase was collected, and the aqueous phase was further extracted with ethyl acetate (50 ml×2). The organic phases together were dehydrated and dried with saturated sodium chloride aqueous solution and anhydrous sodium sulfate in that order, and the solvent was distilled off under reduced pressure, the residual solid was washed with hexane to obtain 1.24 g of the aimed product as white crystal.

Workup

  1. additionafter the completion of the addition
  2. stirringstirred at room temperature for 3 hours
  3. stirringto stir at the same temperature further for 30 minutes
  4. customAfter the completion of the reaction
  5. distillationthe solvent was distilled off under reduced pressure, 50 ml of ethyl acetate and 50 ml of water
  6. additionwere added in the residue
  7. customthe organic phase was collected
  8. extractionthe aqueous phase was further extracted with ethyl acetate (50 ml×2)
  9. dry with materialdried with saturated sodium chloride aqueous solution and anhydrous sodium sulfate in that order
  10. distillationthe solvent was distilled off under reduced pressure
  11. washthe residual solid was washed with hexane

Sources & evidence

ORD record
ord-9e2cf081ee574d2aae04b25afc350467
Source dataset
uspto-grants-2013_07
Patent number
US08492311B2

Reaction notes

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