Acetonitrile → HCID 22265391, compound

HRID 489447Notes

Reaction equation

HRID 489447 reaction equation
[C:1](#[N:3])[CH3:2].[Li]CCCC.[O:9]1[C:13]2([CH2:18][CH2:17][CH2:16][CH2:15][CH:14]2[C:19](OCC)=[O:20])[O:12][CH2:11][CH2:10]1>C1COCC1>[C:1]([CH2:2][C:19]([CH:14]1[CH2:15][CH2:16][CH2:17][CH2:18][C:13]21[O:9][CH2:10][CH2:11][O:12]2)=[O:20])#[N:3]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 336004Ethyl 1,4-dioxaspiro[4.5]decane-6-carboxylateHCID 178418339Butyllithium

Product 1

HCID 22265391HCID 22265391, compoundYield 47.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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. extractionAfter acidification with hydrochloric acid, the mixture was extracted with ethyl acetate
  2. customThe solvent was evaporated under reduced pressure
  3. customthe residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate (10:1))

Sources & evidence

ORD record
ord-8c73ccc253424973b34ce5c35201312d
Source dataset
uspto-grants-2005_12
Patent number
US06977262B2

Reaction notes

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