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 390773Notes

Reaction equation

HRID 390773 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-8d2b45b6baa64776b04b0b2a652090d0
Source dataset
uspto-grants-2013_02
Patent number
US08383659B2

Reaction notes

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