Hydrochloric Acid → 4-[(Cyclohexyl{2-ethyl-5-[4-(trifluoromethyl)phenyl]thiophen-3-yl}methyl)amino]benzoic acid

HRID 1876995ノート

反応式

HRID 1876995 の反応式
Cl[CH:2]([CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1)[C:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[S:5][C:4]=1[CH2:18][CH3:19].[NH2:26][C:27]1[CH:36]=[CH:35][C:30]([C:31]([O:33]C)=[O:32])=[CH:29][CH:28]=1.[I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[NH4+].[OH-].[Na+].Cl>C(OCC)(=O)C.C(O)C.O1CCCC1.CN(C)C(=O)C>[CH:20]1([CH:2]([NH:26][C:27]2[CH:36]=[CH:35][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=2)[C:3]2[CH:7]=[C:6]([C:8]3[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=3)[S:5][C:4]=2[CH2:18][CH3:19])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

参加物

12

反応物 7

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 12082Methyl 4-aminobenzoateHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 685124483-[Chloro(cyclohexyl)methyl]-2-ethyl-5-[4-(trifluoromethyl)phenyl]thiophene

生成物 1

HCID 685081074-[(Cyclohexyl{2-ethyl-5-[4-(trifluoromethyl)phenyl]thiophen-3-yl}methyl)amino]benzoic acid収率 29.3%

試薬・触媒・溶媒 4

HCID 702Ethanol溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒HCID 31374Dimethylacetamide溶媒

反応条件

温度
100 °C

実験手順

To a mixture of 3-[chloro(cyclohexyl)methyl]-2-ethyl-5-[4-(trifluoromethyl)phenyl]thiophene (1.00 g) synthesized above, methyl 4-aminobenzoate (780 mg), sodium iodide (1.55 g) and N,N-dimethylacetamide (10 mL) was added sodium carbonate (547 mg), and the mixture was stirred under an argon atmosphere at 100° C. overnight. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and concentrated under reduced pressure to give a dark-brown oil. To a mixture of the obtained oil, tetrahydrofuran (10 mL) and ethanol (10 mL) was added 1N aqueous sodium hydroxide solution (10 mL), and the mixture was stirred at 60° C. for 1 hr, and stirred with heating under reflux for 30 min. 1N Hydrochloric acid (10 mL) was added to the reaction mixture, the organic solvent was evaporated under reduced pressure, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:7, volume ratio) to give a brown oil. The obtained oil was dissolved in ethyl acetate, washed with 1N hydrochloric acid and brine, dried over magnesium sulfate and concentrated under reduced pressure to give the title compound (369 mg, 29%) as a pale-brown solid.

後処理

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give a dark-brown oil
  8. stirringthe mixture was stirred at 60° C. for 1 hr
  9. stirringstirred
  10. temperaturewith heating
  11. temperatureunder reflux for 30 min
  12. customthe organic solvent was evaporated under reduced pressure
  13. extractionthe mixture was extracted with ethyl acetate
  14. washThe extract was washed with brine
  15. dry with materialdried over magnesium sulfate
  16. concentrationconcentrated under reduced pressure
  17. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:7, volume ratio)
  18. customto give a brown oil
  19. washwashed with 1N hydrochloric acid and brine
  20. dry with materialdried over magnesium sulfate
  21. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-da06bf734a26443f80ff5864abb0318a
出典データセット
uspto-grants-2012_11
特許番号
US08309580B2

反応ノート

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