Sodium ethoxide → 3,4,6,7,8,9-Hexahydropyrido[3,4-b]indolizin-1(2H)-one

Temperature

55 °C

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet was purged with nitrogen and charged with methyl 3-(2-aminoethyl)-5,6,7,8-tetrahydroindolizine-2-carboxylate hydrogen chloride salt 118c (estimated 1.74 mmol, presuming quantitative yield), sodium ethoxide (354 mg, 5.22 mmol) and ethanol (20 mL). The mixture was stirred at 55° C. for 5 h. After that time, the reaction mixture was concentrated under reduced pressure and the residue was partitioned between ethyl acetate (200 mL) and water (100 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford a 67% yield (220 mg) of 118d as a white solid: mp 195-197° C.; 1H NMR (500 MHz, DMSO-d6) d 6.76 (s, 1H), 5.89 (s, 1H), 3.78 (t, 2H, J=6.5 Hz), 3.35 (m, 2H), 2.66 (m, 4H), 1.87 (m, 2H), 1.72 (m, 2H); (APCI+) m/z 191.3 (M+H)

1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet
2. customwas purged with nitrogen
3. concentrationAfter that time, the reaction mixture was concentrated under reduced pressure
4. customthe residue was partitioned between ethyl acetate (200 mL) and water (100 mL)
5. customThe organic layer was separated
6. extractionthe aqueous layer was extracted with ethyl acetate (2×100 mL)
7. washThe combined organic layers were washed with brine
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by column chromatography

ORD record

ord-2a1d1fa98ffc41a4bccce3ceb184fb2a

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618107B2