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

HRID 489446Notes

Reaction equation

HRID 489446 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

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.

Workup

  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))

Sources & evidence

ORD record
ord-17e03e224ab34a289587b47d97e73cb2
Source dataset
uspto-grants-2005_12
Patent number
US06977262B2

Reaction notes

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