Sodium Hydroxide → Methyl 3-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylate

HRID 337013Notes

Reaction equation

HRID 337013 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:13](=O)[CH:14]=[C:15]([C:20]2[CH:25]=[C:24]([Cl:26])[C:23]([F:27])=[C:22]([Cl:28])[CH:21]=2)[C:16]([F:19])([F:18])[F:17])=[C:8]2[CH2:12][CH2:11][CH2:10][C:9]=12)=[O:4].[OH-:30].[Na+].[NH2:32]O.Cl>O.C1COCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:13]2[CH2:14][C:15]([C:20]3[CH:25]=[C:24]([Cl:26])[C:23]([F:27])=[C:22]([Cl:28])[CH:21]=3)([C:16]([F:19])([F:18])[F:17])[O:30][N:32]=2)=[C:8]2[CH2:12][CH2:11][CH2:10][C:9]=12)=[O:4]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 866937493-[3-(3,5-Dichloro-4-fluoro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid methyl ester

Product 1

HCID 71472643Methyl 3-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylateYield 50,384.102%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Stir a mixture of 3-[3-(3,5-Dichloro-4-fluoro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid methyl ester (25 g, 53.6 mmol), NaOH (8.6 g, 0.214 mol) and NH2OH—HCl (7.4 g, 0.107 mmol) in water (100 mL) and THF (200 mL) at room temperature for overnight. After removal of the solvent under vacuum, the solution is diluted with water and extracted with EtOAc (200 mL×3). The combined organic layer is washed with brine, dried over anhydrous Na2SO4 and concentrated by vacuum to afford 3-[5-(3,5-Dichloro-4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid methyl ester as a white solid (26 g), which is used directly in the next step without purification. MS (m/z): 483 (M+1).

Workup

  1. customAfter removal of the solvent under vacuum
  2. additionthe solution is diluted with water
  3. extractionextracted with EtOAc (200 mL×3)
  4. washThe combined organic layer is washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated by vacuum

Sources & evidence

ORD record
ord-1c00a01a8c7540638c1bc885a9caefdf
Source dataset
uspto-grants-2014_11
Patent number
US08889710B2

Reaction notes

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