Ethanol → 8-(2-chlorophenyl)-8-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acid

HRID 1526460Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1526460
C([O:3][C:4](=[O:30])[C:5]([CH3:29])([CH3:28])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH:11]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[Cl:27])[N:12]1[CH2:17][CH2:16][C:15]2[S:18][CH:19]=[CH:20][C:14]=2[CH2:13]1)C.C(O)C.[OH-].[Na+]>O>[Cl:27][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[CH:11]([N:12]1[CH2:17][CH2:16][C:15]2[S:18][CH:19]=[CH:20][C:14]=2[CH2:13]1)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][C:5]([CH3:29])([CH3:28])[C:4]([OH:30])=[O:3]

Komponenten

5

Edukt 3

HCID 702EthanolHCID 14798Sodium HydroxideHCID 569713878-(2-chlorophenyl)-8-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acid ethyl ester

Produkt 1

HCID 569713868-(2-chlorophenyl)-8-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acidAusbeute 43,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

8-(2-Chlorophenyl)-8-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acid ethyl ester (0.86 g, 1.92 mmol) was added to a solution of ethanol (32 mL) and sodium hydroxide (0.53 g, 13.4 mmol) in water (10.4 mL). The mixture was heated to reflux for 6.5 hours. The solution was concentrated under reduced pressure and water (43 mL) was added to the residue. Any starting material was extracted with ethyl acetate/heptane (1/10, 43 mL). The heptane extract was discarded. The remaining aqueous solution was adjusted with 10 N hydrochloric acid solution to pH=6. The product was extracted with CH2Cl2 (3×40 mL), dried over Na2SO4, concentrated and purified by column chromatography (silica gel, ethyl acetate/heptane=1/10 to 1/3) to provide 8-(2-chlorophenyl)-8-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acid (Compound Im, 0.35 g, 43.8% yield, 99.6% purity by HPLC) as a yellow oil. 1H NMR (Field: 300 MHz, Solvent: CDCl3/TMS) δ (ppm): 10.43 (br, 1H), 7.52 (d, 1H, J=7.50 Hz), 7.39 (d, 1H, J=8.10 Hz), 7.28-7.15 (m, 2H), 7.03 (d, 1H, J=5.0 Hz), 6.69 (d, 1H, J=5.0 Hz), 4.24 dd, 1H, J=9.3, 4.2 Hz), 3.83 (d, 1H, J=14.40 Hz), 3.51 (d, 1H, J=14.40 Hz), 2.92-2.73 (m, 4H), 1.99-1.81 (m, 2H), 1.46-1.41 (m, 2H), 1.28-1.15 (m, 6H), 1.13 (s, 6H). (t, 3H, J=7.2 Hz), 1.15-1.08 (m, 2H), 1.07 (s, 6H). 13C NMR (Field: 75 MHz, Solvent: CDCl3/TMS) δ (ppm): 184.02, 138.85, 135.16, 133.87, 133.42, 129.60, 129.17, 128.17, 126.92, 125.52, 122.74, 63.53, 50.54, 47.90, 42.29, 40.70, 32.95, 30.52, 25.75, 25.64, 25.26, 24.96. HRMS (FIA-ESI): Calculated for C23H30ClNO2S (M+H)+: 420.1759. found 420.1779. CHN analysis: Calculated; 65.77; C, 7.20; H, 3.33; N. found; 60.77; C, 6.68; H, 3.11; N. Best fit for CHN: C23H30ClNO2S+HCl

Aufarbeitung

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 6.5 hours
  3. concentrationThe solution was concentrated under reduced pressure and water (43 mL)
  4. additionwas added to the residue
  5. extractionAny starting material was extracted with ethyl acetate/heptane (1/10, 43 mL)
  6. extractionThe heptane extract
  7. extractionThe product was extracted with CH2Cl2 (3×40 mL)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. custompurified by column chromatography (silica gel, ethyl acetate/heptane=1/10 to 1/3)

Quellen und Nachweise

ORD-Eintrag
ord-8facbf83ff5e43268eaffc885d716005
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09085585B2

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