Ammonium Chloride → 4-(1-Methylpiperidin-4-yloxy)-3-trifluoromethylbenzonitrile

HRID 13764

반응식

HRID 13764 반응식
CC(C)([O-])C.[K+].[CH3:7][N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1.F[C:16]1[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][C:17]=1[C:24]([F:27])([F:26])[F:25].[Cl-].[NH4+]>O1CCCC1.O>[CH3:7][N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:16]2[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][C:17]=2[C:24]([F:25])([F:27])[F:26])[CH2:10][CH2:9]1

참가 물질

7

반응물 4

HCID 25517Ammonium ChlorideHCID 660484-Piperidinol, 1-methyl-HCID 1442554-Fluoro-3-(trifluoromethyl)benzonitrileHCID 23665647Potassium tert-butoxide

생성물 1

HCID 231459404-(1-Methylpiperidin-4-yloxy)-3-trifluoromethylbenzonitrile수율 64.8%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매3회

실험 절차

6.68 g of potassium t-butoxide was suspended in 40 ml of anhydrous tetrahydrofuran and a solution of 6.85 g of 1-methyl-4-hydroxypiperidine in 20 ml of anhydrous tetrahydrofuran was added dropwise over 35 minutes while stirring under ice-water cooling and further the mixture was stirred for 30 minutes. On the other hand, 7.50 g of 4-fluoro-3-trifluoromethylbenzonitrile was dissolved in 40 ml of anhydrous tetrahydrofuran, the mixture was stirred under cooling in a dry ice/acetone bath, and the solution prepared earlier was added dropwise at the internal temperature of −70° C. After adding dropwise, the reaction solution was stirred overnight while naturally heating up to room temperature. The reaction solution was ice-cooled, an aqueous saturated ammonium chloride solution and water were added thereto, and then the solvent was distilled off under reduced pressure. The residue was subjected to extraction with ethyl acetate twice. The extracts were washed in turn with water and saturated saline and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain 7.31 g of the objective compound as colorless crystals.

후처리

  1. stirringfurther the mixture was stirred for 30 minutes
  2. stirringthe mixture was stirred
  3. temperatureunder cooling in a dry ice/acetone bath
  4. customthe solution prepared earlier
  5. additionwas added dropwise at the internal temperature of −70° C
  6. additionAfter adding dropwise
  7. stirringthe reaction solution was stirred overnight
  8. temperaturecooled
  9. distillationthe solvent was distilled off under reduced pressure
  10. extractionThe residue was subjected to extraction with ethyl acetate twice
  11. washThe extracts were washed in turn with water and saturated saline
  12. dry with materialdried over anhydrous magnesium sulfate
  13. distillationthe solvent was distilled off under reduced pressure
  14. customThe residue was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-ac5ac920425a4ccd89ccd021d933c772
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07728131B2

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