Ethyl cyanoformate → 5-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carboxylic acid ethyl ester

HRID 242404Notes

Reaction equation

HRID 242404 reaction equation
C([Mg]Cl)C.Br[C:6]1[S:10][C:9]([C:11]2[CH2:15][C:14]([C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=3)([C:16]([F:19])([F:18])[F:17])[O:13][N:12]=2)=[CH:8][C:7]=1[CH3:28].[CH2:29]([O:31][C:32](C#N)=[O:33])[CH3:30]>C1COCC1>[CH2:29]([O:31][C:32]([C:6]1[S:10][C:9]([C:11]2[CH2:15][C:14]([C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=3)([C:16]([F:19])([F:18])[F:17])[O:13][N:12]=2)=[CH:8][C:7]=1[CH3:28])=[O:33])[CH3:30]

Participants

5

Reactant 3

HCID 69336Ethyl cyanoformateHCID 866580393-(5-Bromo-4-methyl-thiophen-2-yl)-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazoleHCID 178461633HCID 178461633, compound

Product 1

HCID 665872885-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carboxylic acid ethyl esterYield 56.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Ethylmagnesium chloride (10.9 ml, 2M in THF) is added over 30 minutes to a solution of 3-(5-bromo-4-methyl-thiophen-2-yl)-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole (10.0 g, Example 2, step D) in THF (15 ml) at 0° C. After 1 hour at room temperature, a solution of ethylcyanoformate (2.81 g) in THF (15 ml) is added to the reaction mixture. After 40 minutes, the reaction is quenched with a saturated aqueous solution of NH4Cl in water. The mixture is extracted three times with MTBE. The organic phases are combined, dried over Na2SO4 and concentrated in vacuo. The crude product is purified on a semi-preparative HPLC to yield 5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carboxylic acid ethyl ester (5.6 g) as a yellowish oil.

Workup

  1. waitAfter 40 minutes
  2. customthe reaction is quenched with a saturated aqueous solution of NH4Cl in water
  3. extractionThe mixture is extracted three times with MTBE
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified on a semi-preparative HPLC

Sources & evidence

ORD record
ord-f5379261f22e403988048c77b786ee43
Source dataset
uspto-grants-2014_02
Patent number
US08653116B2

Reaction notes

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