Diiodomethane → 5-Azaspiro[2.5]octane-5-carboxylic acid, phenylmethyl ester

Temperature

0 °C

To a stirred solution of Diethyl zinc (1.38 g, 11.2 ml, 1 M solution in hexane 11.24 mmol) in dichloromethane (10 ml) was added trifluoroacetic acid (1.28 g, 0.84 ml, 11.24 mmol) drop wise manner at 0° C. Diiodomethane (3.01 g, 0.90 ml, 11.24 mmol) in dichloromethane (5 ml) was added and reaction mixture was stirred at 0° C. for 30 min. A solution of benzyl 3-methylenepiperidine-1-carboxylate (prepared according to the procedure given in European Journal of Medicinal Chemistry 1991, 26, 625-631), (1.3 g, 5.62 mmol) in dichloromethane (10 ml) was added and reaction mixture stirred at 0° C. for 30 min and then at 25° C. for 18 hr. The progress of reaction was monitored by TLC. Reaction mixture was diluted with dichloromethane (25 ml) and poured in to a saturated solution of sodium bicarbonate (50 ml). Solid precipitated out was filtered, organic layer was separated and dried over sodium sulphate and concentrated under reduced pressure to obtain a crude product, which was purified by flash column chromatography using 6% ethyl acetate in hexanes to obtain the title compound (0.95 g, 68.9%). MS: m/z 246 (M+1).

1. customreaction mixture
2. additionwas added
3. customreaction mixture
4. stirringstirred at 0° C. for 30 min
5. waitat 25° C. for 18 hr
6. customThe progress of reaction
7. customReaction mixture
8. customSolid precipitated out
9. filtrationwas filtered
10. customorganic layer was separated
11. dry with materialdried over sodium sulphate
12. concentrationconcentrated under reduced pressure
13. customto obtain a crude product, which
14. customwas purified by flash column chromatography

ORD record

ord-56c81c8878c345d6a6fe0457747d84c6

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09388196B2