Methyl 3-acetyl-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylate → 3-[3-(3,5-Dichloro-4-fluoro-phenyl)-4,4,4-trifluoro-3-hydroxy-butyryl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid methyl ester

HRID 337011

Reaktionsgleichung

Reaktionsgleichung von HRID 337011
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:13](=[O:15])[CH3:14])=[C:8]2[CH2:12][CH2:11][CH2:10][C:9]=12)=[O:4].[Cl:16][C:17]1[CH:18]=[C:19]([C:25](=[O:30])[C:26]([F:29])([F:28])[F:27])[CH:20]=[C:21]([Cl:24])[C:22]=1[F:23]>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:13](=[O:15])[CH2:14][C:25]([C:19]2[CH:20]=[C:21]([Cl:24])[C:22]([F:23])=[C:17]([Cl:16])[CH:18]=2)([OH:30])[C:26]([F:28])([F:27])[F:29])=[C:8]2[CH2:12][CH2:11][CH2:10][C:9]=12)=[O:4]

Komponenten

4

Edukt 2

HCID 71014110Methyl 3-acetyl-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylateHCID 755300231-(3,5-Dichloro-4-fluorophenyl)-2,2,2-trifluoroethanone

Produkt 1

HCID 866937483-[3-(3,5-Dichloro-4-fluoro-phenyl)-4,4,4-trifluoro-3-hydroxy-butyryl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid methyl esterAusbeute 89,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

Add a solution of LiHDMS (1M in THF, 75 mL, 75 mmol) to a suspension of 3-acetyl-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid methyl ester (14.0 g, 62.5 mmol) in dry THF (200 mL) at −78° C. under N2. After stirring at room temperature for 1.5 h, add 1-(3,5-dichloro-4-fluoro-phenyl)-2,2,2-trifluoro-ethanone (17.9 g, 68.7 mmol) in dry THF (100 mL) to the reaction mixture and stir the resultant mixture at the same temperature for additional 2 hours. Quench the reaction with saturated NH4Cl aqueous solution. Extract the aqueous mixture with EtOAc (100 mL×3). The combined organic layers are washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum. Purify the residue by silica gel chromatograph (PE:EtOAc 15:1) to afford 3-[3-(3,5-Dichloro-4-fluoro-phenyl)-4,4,4-trifluoro-3-hydroxy-butyryl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid methyl ester as an orange solid (27 g, 89.3%). MS (m/z): 486 (M+1).

Aufarbeitung

  1. customQuench
  2. customthe reaction with saturated NH4Cl aqueous solution
  3. extractionExtract the aqueous mixture with EtOAc (100 mL×3)
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under vacuum
  7. customPurify the residue by silica gel chromatograph (PE:EtOAc 15:1)

Quellen und Nachweise

ORD-Eintrag
ord-c9612e50944242dcaa55aee45a9052cd
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889710B2

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