Hydrochloric Acid → 5-[4-(4-Ethoxy2,3-difluorophenoxymethyl)cyclohexyl]tetrahydropyran-2-one

HRID 605452노트

반응식

HRID 605452 반응식
C(O)C.C([BH3-])#N.[Na+].[CH2:8]([O:10][C:11]1[CH:34]=[CH:33][C:14]([O:15][CH2:16][CH:17]2[CH2:22][CH2:21][CH:20]([CH:23](C=O)[CH2:24][CH2:25][C:26]([O:28][CH2:29]C)=[O:27])[CH2:19][CH2:18]2)=[C:13]([F:35])[C:12]=1[F:36])[CH3:9].Cl>O>[CH2:8]([O:10][C:11]1[CH:34]=[CH:33][C:14]([O:15][CH2:16][CH:17]2[CH2:22][CH2:21][CH:20]([CH:23]3[CH2:29][O:28][C:26](=[O:27])[CH2:25][CH2:24]3)[CH2:19][CH2:18]2)=[C:13]([F:35])[C:12]=1[F:36])[CH3:9]

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 5003444Sodium cyanoborohydrideHCID 86635748Ethyl 4-[4-(4-ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]5-oxopentanoate

생성물 1

HCID 668767205-[4-(4-Ethoxy2,3-difluorophenoxymethyl)cyclohexyl]tetrahydropyran-2-one수율 93.3%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

In a reactor under nitrogen atmosphere, 20 mL of ethanol and 0.4 g of sodium cyanoborohydride were added to 5.4 g of ethyl 4-[4-(4-ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]5-oxopentanoate obtained in the eleventh step, and pH of the mixture was adjusted to about 3 with hydrochloric acid (2M), followed by stirring at room temperature for 15 hours. 30 mL of water was added to the reaction solution, which was extracted three times with 20 mL of toluene. The mixture including the organic layer was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was placed in a flask equipped with a Dean-Stark apparatus, to which 100 mL of toluene and 0.1 g of p-toluenesulfonic acid monohydrate were added, and the mixture was refluxed for 1 hour while the solvent was distilled off with the Dean-Stark apparatus. The solution was cooled to room temperature, washed with water, and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to provide 4.5 g of 5-[4-(4-ethoxy2,3-difluorophenoxymethyl)cyclohexyl]tetrahydropyran-2-one.

후처리

  1. customobtained in the eleventh step, and pH of the mixture
  2. extractionwas extracted three times with 20 mL of toluene
  3. washwas washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe residue was placed in a flask
  7. customequipped with a Dean-Stark apparatus, to which 100 mL of toluene and 0.1 g of p-toluenesulfonic acid monohydrate
  8. additionwere added
  9. temperaturethe mixture was refluxed for 1 hour while the solvent
  10. distillationwas distilled off with the Dean-Stark apparatus
  11. temperatureThe solution was cooled to room temperature
  12. washwashed with water
  13. dry with materialdried over anhydrous magnesium sulfate
  14. distillationthe solvent was distilled off under reduced pressure
  15. customThe residue was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-c2f53a64b8e04de69a09b4358c85e0c0
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07914862B2

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