Hydrochloric Acid → tert-Butyl 4-(6-formylpyridin-3-yl)piperazine-1-carboxylate

HRID 1465469Notes

Reaction equation

[C:1]([C:3]1[N:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#N.C1(C)C=CC=CC=1.[H-].C([Al+]CC(C)C)C(C)C.Cl.C(=O)([O-])[O-:41].[Na+].[Na+]>ClCCl>[CH:1]([C:3]1[N:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)=[O:41]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of tert-butyl 4-(6-cyanopyridin-3-yl)piperazine-1-carboxylate (144.2 mg, 0.500 mmol) in anhydrous dichloromethane (5 ml) was added dropwise at −78° C. 1.5M diisobutylaluminum hydride toluene solution (0.4 ml, 0.6 mmol) over 5 mins. After stirring at −78° C. for 1.5 hrs, 1M hydrochloric acid (1 ml) was added. The mixture was heated to room temperature and stirred for 1 hr. Saturated aqueous sodium carbonate solution was added, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=2:3) to give tert-butyl 4-(6-formylpyridin-3-yl)piperazine-1-carboxylate (73.4 mg, yield 50.4%) as a slightly yellow solid.

Workup

temperatureThe mixture was heated to room temperature
stirringstirred for 1 hr
extractionthe mixture was extracted with dichloromethane
dry with materialThe organic layer was dried over anhydrous magnesium sulfate
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=2:3)

Sources & evidence

ORD record: ord-86b9c61b91554a86af3c91140af16bee
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08999989B2

Reaction notes

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