2,2,6,6-Tetramethyl-4-piperidone → (2,2,6,6-Tetramethylpiperidin-4-ylidene)acetonitrile

HRID 1986175Notes

Reaction equation

CC(C)([O-])C.[K+].C(OP([CH2:15][C:16]#[N:17])(=O)OCC)C.[CH3:18][C:19]1([CH3:28])[CH2:24][C:23](=O)[CH2:22][C:21]([CH3:27])([CH3:26])[NH:20]1>C1COCC1>[CH3:18][C:19]1([CH3:28])[CH2:24][C:23](=[CH:15][C:16]#[N:17])[CH2:22][C:21]([CH3:27])([CH3:26])[NH:20]1

Participants

Conditions

Temperature: 0 °C

Procedure

Potassium tert-butoxide (9.40 g, 83.7 mmol) is suspended in THF (175 mL), then cooled to 0° C. Cyanomethyl-phosphonic acid diethyl ester (16.0 g, 90.2 mmol) is added over five minutes. After stirring for 20 minutes, 2,2,6,6-tetramethylpiperidin-4-one (10.0 g, 64.4 mmol) dissolved in THF (50 mL) is added to the reaction mixture at −78° C. After the addition is complete the cold bath is removed. The reaction is stirred overnight, then enough water is added to dissolve any suspended salts. The organic layer is separated and the aqueous layer is extracted with EtOAc. The organic layers are combined, concentrated, then the residue is chromatographed on silica gel, eluting with 0-3% 2M NH3/MeOH in dichloromethane to give 3.77 g of (2,2,6,6-tetramethylpiperidin-4-ylidene)-acetonitrile (33% yield).

Workup

additionis added to the reaction mixture at −78° C
additionAfter the addition
customis removed
stirringThe reaction is stirred overnight
additionenough water is added
dissolutionto dissolve any suspended salts
customThe organic layer is separated
extractionthe aqueous layer is extracted with EtOAc
concentrationconcentrated
customthe residue is chromatographed on silica gel
washeluting with 0-3% 2M NH3/MeOH in dichloromethane

Sources & evidence

ORD record: ord-fa328967377e41c983d2c4c22ddc0373
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07547691B2

Reaction notes

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