Hydrochloric Acid → Methyl 2-[(5-cyanopyridin-3-yl)methyl]-3-oxobutanoate

HRID 45240Notes

Reaction equation

[H-].[Na+].[C:3]([O:9][CH3:10])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].Cl[CH2:12][C:13]1[CH:14]=[C:15]([C:19]#[N:20])[CH:16]=[N:17][CH:18]=1.Cl>COCCOC.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[C:19]([C:15]1[CH:14]=[C:13]([CH2:12][CH:4]([C:5](=[O:6])[CH3:7])[C:3]([O:9][CH3:10])=[O:8])[CH:18]=[N:17][CH:16]=1)#[N:20]

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of 84 mg (2.11 mmol) of sodium hydride (60% in oil) in 3 mL of anhydrous DME is added, under argon at 0° C., 0.23 ml (2.11 mmol) of methyl acetoacetate. The reaction medium is stirred for 30 minutes at 0° C. and for 30 minutes at room temperature, followed by addition of 161 mg (1.06 mmol) of 5-(chloromethyl)pyridine-3-carbonitrile diluted in 1 mL of DME and 29 mg (0.11 mmol) of tetrabutylammonium iodide. The medium is then heated at 65° C. for 4 hours. After cooling to room temperature, the medium is taken up in 10 mL or water, neutralized by adding 0.1N HCl, and then extracted with EtOAc (2×40 mL), dried over Na2SO4, concentrated under reduced pressure and purified by chromatography on a column of silica gel, eluting with a cyclohexane/EtOAc mixture (8/2). 140 mg of methyl 2-[(5-cyanopyridin-3-yl)methyl]-3-oxobutanoate are obtained in the form of a colourless oil.

Workup

additionis added, under argon at 0° C.
temperatureThe medium is then heated at 65° C. for 4 hours
temperatureAfter cooling to room temperature
extractionextracted with EtOAc (2×40 mL)
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure
custompurified by chromatography on a column of silica gel
washeluting with a cyclohexane/EtOAc mixture (8/2)

Sources & evidence

ORD record: ord-e81c05e59b8547d083b304075958f09f
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08541455B2

Reaction notes

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