Acetic Acid → TERT-BUTYL 4-(1-CYANO-2-ETHOXY-2-OXOETHYLIDENE)PIPERIDINE-1-CARBOXYLATE

HRID 1752314Notes

Reaction equation

[C:1]([CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].C([O-])(=O)C.[NH4+].C(O)(=O)C.[C:18]([N:25]1[CH2:30][CH2:29][C:28](=O)[CH2:27][CH2:26]1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>C1(C)C=CC=CC=1>[C:1]([C:3](=[C:28]1[CH2:29][CH2:30][N:25]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:26][CH2:27]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2]

Participants

Conditions

Temperature: 85 °C

Procedure

Ethyl cyanoacetate (3.475 mL, 1.3 equiv), ammonium acetate (1.16 g, 0.6 equiv), acetic acid (1.725 mL, 1.2 equiv) were added to a solution of N-Boc-4-piperidone (5 g, 25.11 mmol) in toluene (55 mL). The mixture was heated at 110° C. for 2 h, 85° C. overnight, then at 135° C. for 4 h. The mixture was washed with 5% aq NaOH (15 mL), water (15 mL) and brine (10 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by chromatography on a 120-g silica gel cartridge, eluted with a 5 to 40% EtOAc in hexanes gradient, to afford tert-butyl 4-(1-cyano-2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate (4.71 g, 64%) as an off-white solid.

Workup

washThe mixture was washed with 5% aq NaOH (15 mL), water (15 mL) and brine (10 mL)
dry with materialdried over Na2SO4
filtrationAfter filtration and concentration
customthe residue was purified by chromatography on a 120-g silica gel cartridge
washeluted with a 5 to 40% EtOAc in hexanes gradient

Sources & evidence

ORD record: ord-3cf611d45c57461e838ecf2868b4df01
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09163012B2

Reaction notes

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