Ethylene Glycol → Ethyl 1,4-dioxaspiro[4.5]decane-6-carboxylate

HRID 489446노트

반응식

HRID 489446 반응식
[CH3:1][CH2:2][O:3][C:4]([CH:6]1[C:11](=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5].[CH2:13](O)[CH2:14][OH:15].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[O:15]1[C:11]2([CH2:10][CH2:9][CH2:8][CH2:7][CH:6]2[C:4]([O:3][CH2:2][CH3:1])=[O:5])[O:12][CH2:13][CH2:14]1

참가 물질

5

반응물 3

HCID 174Ethylene GlycolHCID 6101p-Toluenesulfonic acidHCID 95543Ethyl 2-oxocyclohexanecarboxylate

생성물 1

HCID 336004Ethyl 1,4-dioxaspiro[4.5]decane-6-carboxylate수율 98.5%

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

To a solution of ethyl 2-cyclohexanonecarboxylate (25 g) in toluene (200 mL) was added ethyleneglycol (10.1 g) and p-toluenesulfonic acid (2.8 g) at room temperature and the mixture was heated under reflux with Dean-Stark apparatus for five hours. The reaction mixture was cooled to room temperature, the solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate (10:1)) to give ethyl 1,4-dioxa-spiro[4,5]decane-6-carboxylate (31 g) as a colorless oil. To a solution of acetonitrile (7.2 g) in THF (700 mL) was added n-BuLi (160 mmol) at −78° C. Further, ethyl 1,4-dioxa-spiro[4,5]decane-6-carboxylate (31 g) was added and the mixture was stirred for an hour. After acidification with hydrochloric acid, the mixture was extracted with ethyl acetate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate (10:1)) to give 1-cyano-2-(1,4-dioxa-spiro[4,5]decan-6-yl)ethan-2-one (14.5 g) as a colorless oil. A solution of 2,1,3-benzoxadiazole-4-aldehyde (0.8 g), 3-aminopyrazole (0.5 g) and 1-cyano-2-(1,4-dioxa-spiro[4,5]-decan-6-yl)ethan-2-one (1.2 g) in acetonitrile (10 mL) was heated under reflux overnight. The reaction mixture was cooled to room temperature, and the precipitated crystals were collected by filtration to give 4-(2,1,3-benzoxadiazol-4-yl)-5-cyano-4,7-dihydro-6-(1,4-dioxa-spiro[4,5]decan-6-yl)-2H-pyrazolo[3,4-b]pyridine (1.3 g) as colorless crystals.

후처리

  1. temperaturethe mixture was heated
  2. temperatureunder reflux with Dean-Stark apparatus for five hours
  3. customthe solvent was evaporated under reduced pressure
  4. customthe residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate (10:1))

출처 및 근거

ORD 기록
ord-17e03e224ab34a289587b47d97e73cb2
출처 데이터셋
uspto-grants-2005_12
특허 번호
US06977262B2

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