Sodium Hydroxide → 4-({Cyclohexyl[2-ethyl-5-(1-hydroxy-2-methylpropyl)thiophen-3-yl]methyl}amino)benzoic acid

HRID 1877271노트

반응식

HRID 1877271 반응식
[CH:1]1([CH:7]([NH:17][C:18]2[CH:27]=[CH:26][C:21]([C:22]([O:24]C)=[O:23])=[CH:20][CH:19]=2)[C:8]2[CH:12]=[C:11]([CH:13]=[O:14])[S:10][C:9]=2[CH2:15][CH3:16])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:28]([Mg]Br)([CH3:30])[CH3:29].O1CCCC1.[Cl-].[NH4+].[OH-].[Na+]>O1CCCC1.C(O)C>[CH:1]1([CH:7]([NH:17][C:18]2[CH:27]=[CH:26][C:21]([C:22]([OH:24])=[O:23])=[CH:20][CH:19]=2)[C:8]2[CH:12]=[C:11]([CH:13]([OH:14])[CH:28]([CH3:30])[CH3:29])[S:10][C:9]=2[CH2:15][CH3:16])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

참가 물질

7

반응물 4

HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 86646397Methyl 4-{[cyclohexyl(2-ethyl-5-formylthiophen-3-yl)methyl]amino}benzoateHCID 178420663HCID 178420663, 화합물

생성물 1

HCID 685143814-({Cyclohexyl[2-ethyl-5-(1-hydroxy-2-methylpropyl)thiophen-3-yl]methyl}amino)benzoic acid수율 60%

시약·촉매·용매 2

HCID 702Ethanol용매HCID 8028Tetrahydrofuran용매2회

실험 절차

To a solution of methyl 4-{[cyclohexyl(2-ethyl-5-formylthiophen-3-yl)methyl]amino}benzoate (540 mg) synthesized in Example 287 (6) in tetrahydrofuran (10 mL) was added dropwise 1.0M isopropylmagnesium bromide-tetrahydrofuran solution (3.50 mL) at −45° C., and the mixture was stirred for 3 hr. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (25% ethyl acetate/hexane) to give a yellow oil. To a mixture of the obtained oil, tetrahydrofuran (5 mL) and ethanol (5 mL) was added 1N aqueous sodium hydroxide solution (5 mL), and the mixture was stirred with heated under reflux for 5 hr, and concentrated under reduced pressure. The residue was dissolved in water (10 mL), and 1N hydrochloric acid (5 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title compound (350 mg, 60%) as a pale-yellow solid. The obtained resultant product was a mixture of two diastereomers (about 2:3).

후처리

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (25% ethyl acetate/hexane)
  8. customto give a yellow oil
  9. stirringthe mixture was stirred
  10. temperaturewith heated
  11. temperatureunder reflux for 5 hr
  12. concentrationconcentrated under reduced pressure
  13. dissolutionThe residue was dissolved in water (10 mL)
  14. addition1N hydrochloric acid (5 mL) was added at 0° C
  15. filtrationThe resulting precipitate was collected by filtration

출처 및 근거

ORD 기록
ord-8d2f7d6d39604ac6a6dd876369117e21
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08309580B2

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