4-Toluenesulfonyl chloride → {6-Fluoro-4-[1-(toluene-4-sulfonyl)-piperidin-4-yl]-naphthalen-2-yl}-acetic acid methyl ester

HRID 2363826Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2363826
C(N(C(C)C)CC)(C)C.FC(F)(F)C(O)=O.[CH3:17][O:18][C:19](=[O:38])[CH2:20][C:21]1[CH:30]=[C:29]([CH:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([F:37])[CH:27]=2)[CH:22]=1.[C:39]1([CH3:49])[CH:44]=[CH:43][C:42]([S:45](Cl)(=[O:47])=[O:46])=[CH:41][CH:40]=1>O1CCCC1>[CH3:17][O:18][C:19](=[O:38])[CH2:20][C:21]1[CH:30]=[C:29]([CH:31]2[CH2:36][CH2:35][N:34]([S:45]([C:42]3[CH:43]=[CH:44][C:39]([CH3:49])=[CH:40][CH:41]=3)(=[O:47])=[O:46])[CH2:33][CH2:32]2)[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([F:37])[CH:27]=2)[CH:22]=1

Komponenten

5

Edukt 3

HCID 73974-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 86686887HCID 86686887, Verbindung

Produkt 1

HCID 86686893{6-Fluoro-4-[1-(toluene-4-sulfonyl)-piperidin-4-yl]-naphthalen-2-yl}-acetic acid methyl esterAusbeute 46,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Diisopropylethylamine (0.6 mL, 3.4 mmol) was added at 0° C. to a solution of (6-fluoro-4-piperidin-4-yl-naphthalen-2-yl)-acetic acid methyl ester trifluoroacetate salt (which may be prepared as described above; 150 mg, 0.36 mmol) in tetrahydrofuran (5 mL), and the mixture was stirred at room temperature for 30 min. p-Toluenesulfonyl chloride (available from Sigma-Aldrich; 103 mg, 0.54 mmol) was added and the mixture was stirred at room temperature for 16 h. The solvent was evaporated under reduced pressure. Ethyl acetate was added and the mixture was washed with aqueous NaHCO3 (5 mL) and water (5 mL). The organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by chromatography on silica gel using a Biotage purification system, eluting with 12% ethyl acetate/hexanes, to give {6-fluoro-4-[1-(toluene-4-sulfonyl)-piperidin-4-yl]-naphthalen-2-yl}-acetic acid methyl ester (76 mg, 46%) as a white solid. MS cald. for C24H25FNO4S [(M+H)+]: 456, obsd. 456.4.

Aufarbeitung

  1. additionwas added
  2. customThe solvent was evaporated under reduced pressure
  3. additionEthyl acetate was added
  4. washthe mixture was washed with aqueous NaHCO3 (5 mL) and water (5 mL)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe residue was purified by chromatography on silica gel using
  9. customa Biotage purification system
  10. washeluting with 12% ethyl acetate/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-cdda0993e8f44da1b0450786c1c810b3
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08691993B2

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