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

HRID 1526459ノート

反応式

HRID 1526459 の反応式
Cl.[S:2]1[C:10]2[CH2:9][CH2:8][NH:7][CH2:6][C:5]=2[CH:4]=[CH:3]1.[OH-].[Na+].S1C2CCNCC=2C=C1.[CH2:22]([O:24][C:25](=[O:43])[C:26]([CH3:42])([CH3:41])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH:32](Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[Cl:39])[CH3:23].C(=O)([O-])[O-].[K+].[K+]>O.CN(C=O)C>[CH2:22]([O:24][C:25](=[O:43])[C:26]([CH3:42])([CH3:41])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH:32]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[Cl:39])[N:7]1[CH2:8][CH2:9][C:10]2[S:2][CH:3]=[CH:4][C:5]=2[CH2:6]1)[CH3:23]

参加物

8

反応物 5

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 30850764,5,6,7-Tetrahydrothieno(3,2-c)pyridineHCID 101763424,5,6,7-Tetrahydrothieno(3,2-c)pyridinium chlorideHCID 675129798-Bromo-8-(2-chlorophenyl)-2,2-dimethyloctanoic acid ethyl ester

生成物 1

HCID 569713878-(2-chlorophenyl)-8-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acid ethyl ester収率 43.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 6228Dimethylformamide溶媒

反応条件

温度
67.5 °C

実験手順

4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride (1.30 g, 7.19 mmol) was added to sodium hydroxide (1.38 g) in water (86 mL) and extracted with dichloromethane (3×20 mL). The dichloromethane was dried over sodium sulfate, filtered, and concentrated to prepare the free base (1.0 g). 4,5,6,7-Tetrahydrothieno[3,2-c]pyridine free base (1.0 g, 7.19 mmol) and 8-bromo-8-(2-chlorophenyl)2,2-dimethyloctanoic acid ethyl ester (2.8 g, 7.19 mmol) were dissolved in DMF (75 mL) with potassium carbonate (1.49 g, 10.79 mmol). The mixture was heated to 65-70° C. overnight. After 18 hours, the mixture was cooled to room temperature and water (50 mL) was added. The product was extracted with diethyl ether (3×50 mL). The combined organic extracts were washed with water (3×50 mL), dried over sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel, eluting with ethyl acetate/heptane (1/10) to provide 8-(2-chlorophenyl)-8-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acid ethyl ester (Compound In, 1.4 g, 43.5%) as a yellow oil. 1H NMR (Field: 300 MHz, Solvent: CDCl3/TMS) δ (ppm): 7.49 (dd, 1H, J=7.5, 1.5 Hz), 7.35 (dd, 1H, J=8.1, 1.2 Hz), 7.24 (dt, 1H, J=7.5, 1.0 Hz), 7.16 (dt, 1H, J=7.8, 1.5 Hz), 7.02 (d, 1H, J=5.0 Hz), 6.68 (d, 1H, J=5.0 Hz), 4.18 (dd, 1H, J=8.7, 4.2 Hz), 4.08 (q, 2H, J=6.9 Hz), 3.82 (d, 1H, J=14.1 Hz), 3.48 (d, 1H, J=14.1 Hz), 2.88-2.66 (m, 4H), 1.96-1.76 (m, 2H), 1.46-1.41 (m, 2H), 1.26-1.18 (m, 6H), 1.21 (t, 3H, J=6.9 Hz), 1.11 (s, 6H). 13C NMR (Field: 75 MHz, Solvent: CDCl3/TMS) δ (ppm): 177.92, 134.92, 134.21, 133.53, 129.48, 129.06, 127.94, 126.77, 125.44, 122.60, 63.67, 60.27, 50.73, 48.08, 42.29, 40.85, 33.02, 30.52, 26.13, 25.39, 25.01, 14.51. HRMS (FIA-ESI-TOFM): Calculated for C25H34ClNO2S (M+H)+: 448.2072. found 448.2067.

後処理

  1. extractionextracted with dichloromethane (3×20 mL)
  2. dry with materialThe dichloromethane was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto prepare the free base (1.0 g)
  6. temperaturethe mixture was cooled to room temperature
  7. extractionThe product was extracted with diethyl ether (3×50 mL)
  8. washThe combined organic extracts were washed with water (3×50 mL)
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product was purified by column chromatography on silica gel
  12. washeluting with ethyl acetate/heptane (1/10)

出典と根拠

ORDレコード
ord-1cf9e4afae824fd8a9ddbf493f944a43
出典データセット
uspto-grants-2015_07
特許番号
US09085585B2

反応ノート

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