Hydrochloric Acid → Octahydroindolizin-7-one

HRID 1918484Notes

Reaction equation

C(O[CH:4](OCC)[CH2:5][CH2:6][CH2:7][NH2:8])C.[CH:12]([C:14]([CH3:16])=[O:15])=[CH2:13].Cl>CCOCC>[CH2:5]1[CH:4]2[N:8]([CH2:13][CH2:12][C:14](=[O:15])[CH2:16]2)[CH2:7][CH2:6]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 4-aminobutyraldehyde diethyl acetal (2.51 mL, 14.3 mmol) in Et2O (5 mL) was added methyl vinyl ketone (1.21 mL, 14.3 mmol). After 1 h, concentrated HCl (5 mL) was added, and the reaction mixture was heated at 100° C. for 2 h. The mixture was concentrated to give hexahydroindolizin-7(1H)-one, which was carried forward without purification. The crude residue was diluted with EtOH (5 mL), and 3-bromophenylhydrazine hydrochloride (1.02 g, 4.47 mmol) was added followed by concentrated HCl (5 mL). The reaction mixture was heated at reflux overnight. After the mixture was concentrated, the residue was purified by flash column chromatography (silica gel, 5% CH3OH in CH2Cl2) to give the title compound (0.15 g, 12%) as a yellow solid: 1H NMR (300 MHz, DMSO-d6) δ 10.95 (s, 1H), 7.43-7.42 (d, J=1.6 Hz, 1H), 7.29-7.26 (d, J=8.3 Hz, 1H), 7.03-7.03 (dd, J=8.4, 1.8 Hz, 1H), 4.10-4.05 (d, J=13.4 Hz, 1H), 3.22-3.14 (m, 2H), 2.92-2.88 (d, J=13.7 Hz, 1H), 2.57-2.40 (m, 2H), 2.32-2.22 (m, 1H), 2.09-1.98 (m, 1H), 1.88-1.75 (m, 2H), 1.57-1.53 (m, 1H); ESI MS m/z 291 [M+H]+.

Workup

concentrationThe mixture was concentrated

Sources & evidence

ORD record: ord-5a5018a46d164bedba4080180f1dc1ec
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08618299B2

Reaction notes

Loading…