Potassium Carbonate → HCID 66740038, Verbindung

HRID 1627258Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1627258
[F:1][C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([F:21])[C:14]=1[CH2:15]OS(C)(=O)=O)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[Cl:22][C:23]1[CH:24]=[C:25]([C:30]([C:33]2[N:37]([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[C:40]([O:45][CH3:46])[CH:39]=3)[C:36]([SH:47])=[N:35][CH:34]=2)([CH3:32])[CH3:31])[CH:26]=[CH:27][C:28]=1[Cl:29].C([O-])([O-])=O.[K+].[K+]>CC(C)=O.CCOC(C)=O.O>[Cl:22][C:23]1[CH:24]=[C:25]([C:30]([C:33]2[N:37]([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[C:40]([O:45][CH3:46])[CH:39]=3)[C:36]([S:47][CH2:15][C:14]3[C:13]([F:21])=[CH:12][C:4]([C:5]([O:7][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:6])=[CH:3][C:2]=3[F:1])=[N:35][CH:34]=2)([CH3:32])[CH3:31])[CH:26]=[CH:27][C:28]=1[Cl:29]

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 86662220Tert-butyl 3,5-difluoro-4-((methylsulfonyloxy)methyl)benzoateHCID 178492989HCID 178492989, Verbindung

Produkt 1

HCID 66740038HCID 66740038, VerbindungAusbeute 87 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 180AcetoneLösungsmittel2×HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of tert-butyl 3,5-difluoro-4-((methylsulfonyloxy)methyl)benzoate (355 mg, 1.10 mmol) and 5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazole-2-thiol (402 mg, 0.98 mmol)—prepared in a manner similar to that described for Example 3 from commercially available reagents—was suspended in acetone (4 mL) and treated with K2CO3 (223 mg, 1.6 mmol). The resulting white suspension was stirred at ambient temperature. The reaction mixture rapidly became a thick slurry, and acetone (5 mL) was added to facilitate stirring. After 75 min, the reaction was diluted with EtOAc and water. The aqueous layer was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to afford crude product that was purified by flash chromatography (silica gel, EtOAc/Hex, 0:100 to 80:20) to afford the title compound (541 mg, 87% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.49-7.40 (m, 2H), 7.30-7.24 (m, 1H), 7.19 (s, 1H), 7.10 (d, J=2.2 Hz, 1H), 6.87 (ddd, J=10.7, 9.5, 5.4 Hz, 2H), 6.28 (ddd, J=8.5, 3.8, 2.5 Hz, 1H), 5.85 (dd, J=7.5, 2.4 Hz, 1H), 4.20-4.07 (m, 2H), 3.46 (s, 3H), 1.57 (s, 9H), 1.54 (s, 3H), 1.46 (s, 3H); MS (EI) m/z 637 (MH+).

Aufarbeitung

  1. additionwas added
  2. stirringto facilitate stirring
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto afford crude product that
  8. customwas purified by flash chromatography (silica gel, EtOAc/Hex, 0:100 to 80:20)

Quellen und Nachweise

ORD-Eintrag
ord-fa9604d69aad40b7b1c1923ae5edbb25
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785488B2

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