Formamide → tert-Butyl 4-(3-carbamoylpropyl)piperidine-1-carboxylate

HRID 2376847Notes

Reaction equation

C([O:3][C:4]([CH2:6][CH2:7][CH2:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1)=O)C.C([NH2:24])=O.[O-]CC.[Na+]>CN(C)C=O>[C:4]([CH2:6][CH2:7][CH2:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1)(=[O:3])[NH2:24]

Participants

Conditions

Temperature: 100 °C

Procedure

tert-Butyl 4-(3-ethoxycarbonylpropyl)piperidine-1-carboxylate (0.60 g, 2.0 mmol, the product of Production example 43-1) and formamide (0.27 ml, 6.7 mmol) were dissolved in N,N-dimethylformamide (1.0 ml); sodium ethoxide (0.095 g, 1.4 mmol) was added thereto while stirred and heated at 100° C.; the reaction mixture was stirred for 2 hours under nitrogen atmosphere. After cooled to room temperature, the reaction mixture was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (eluent; hexane-ethyl acetate=95:5 to 85:15). The title compound was obtained as a colorless oil (0.38 g, 1.4 mmol, 70%).

Workup

stirringthe reaction mixture was stirred for 2 hours under nitrogen atmosphere
temperatureAfter cooled to room temperature
customthe reaction mixture was partitioned between water and ethyl acetate
washThe organic layer was washed with brine
dry with materialdried over anhydrous magnesium sulfate
distillationthe solvent was distilled off under reduced pressure
customThe residue was purified by silica gel chromatography (eluent; hexane-ethyl acetate=95:5 to 85:15)

Sources & evidence

ORD record: ord-b4bbc7928653456d85b4e6d2a5037635
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07468380B2

Reaction notes

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