Ammonium Chloride → 1-(4-Ethoxy-2,3-difluorophenyl)-4-(3-propylcyclopentyl)cyclohexanol

HRID 1464847노트

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HRID 1464847 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH3:10])=[C:4]([F:11])[C:3]=1[F:12].C([Li])CCC.[CH2:18]([CH:21]1[CH2:25][CH2:24][CH:23]([CH:26]2[CH2:31][CH2:30][C:29](=[O:32])[CH2:28][CH2:27]2)[CH2:22]1)[CH2:19][CH3:20].[Cl-].[NH4+]>C1COCC1.CCCCCC>[CH2:9]([O:8][C:5]1[CH:6]=[CH:7][C:2]([C:29]2([OH:32])[CH2:28][CH2:27][CH:26]([CH:23]3[CH2:24][CH2:25][CH:21]([CH2:18][CH2:19][CH3:20])[CH2:22]3)[CH2:31][CH2:30]2)=[C:3]([F:12])[C:4]=1[F:11])[CH3:10]

참가 물질

7

반응물 4

HCID 25517Ammonium ChlorideHCID 269854911-Bromo-4-ethoxy-2,3-difluorobenzeneHCID 679922824-(3-Propylcyclopentyl)-cyclohexanoneHCID 178418339Butyllithium

생성물 1

HCID 679923521-(4-Ethoxy-2,3-difluorophenyl)-4-(3-propylcyclopentyl)cyclohexanol수율 94.7%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8058Hexane용매

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온도
-78 °C

실험 절차

THF (100 ml) was added to 1-bromo-4-ethoxy-2,3-difluorobenzene (5.1 g) in a reaction vessel under an atmosphere of nitrogen, and the mixture was cooled to −78° C. n-Butyllithium (1.57 M, in a hexane solution) (13.8 ml) was added dropwise at a temperature of −70° C. or lower. The stirring was continued at −78° C. for another 2 hours, and 4-(3-propylcyclopentyl)-cyclohexanone (3.0 g) in a THF (10 ml) solution was added dropwise at a temperature of −70° C. or lower. After the mixture had been stirred at −78° C. for another 1 hour, it was warmed to room temperature, and a saturated aqueous solution of ammonium chloride (50 ml) was added. The mixture was separated, and the water layer was extracted with ethyl acetate three times, and then the combined organic layer was washed with brine. The solution was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (eluent: ethyl acetate/n-heptane=1/9 by volume) to give 1-(4-ethoxy-2,3-difluorophenyl)-4-(3-propylcyclopentyl)cyclohexanol (5.0 g).

후처리

  1. temperatureit was warmed to room temperature
  2. customThe mixture was separated
  3. extractionthe water layer was extracted with ethyl acetate three times
  4. washthe combined organic layer was washed with brine
  5. dry with materialThe solution was dried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was purified by silica gel chromatography (eluent: ethyl acetate/n-heptane=1/9 by volume)

출처 및 근거

ORD 기록
ord-827e5e7f239840f2b27cb68413de5dcc
출처 데이터셋
uspto-grants-2015_04
특허 번호
US08999197B2

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