Hydrochloric Acid → 2-(tert-Butoxycarbonyl)octahydrocyclopenta[c]pyrrole-5-carboxylic acid

To the diethyl 3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]octane-7,7-dicarboxylate (10.5 g, 29.5 mmol) was added water (25 mL) and concentrated (12 N) hydrochloric acid (75 mL). The mixture was heated at reflux for 8 h. The volatiles were evaporated, and the residue was dissolved in water (10 mL) and the pH of the solution was adjusted to pH 8 with 10% aqueous sodium bicarbonate. Di-tert-butyl dicarbonate (8.5 g, 39 mmol) in tert-butanol (60 mL) was added and the reaction was stirred overnight at ambient temperature. Ethyl acetate (100 mL) was added to the reaction and the pH of the solution was adjusted to pH 3 with 2 M aqueous hydrochloric acid. The aqueous layer was extracted with ethyl acetate (200 mL). The organic layer was washed with water (2×200 mL) and brine (100 mL), dried (anhydrous sodium sulfate), concentrated (rotary evaporation), and purified by silica gel column chromatography to give 5.1 g of 3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]octane-7-carboxylic acid, as a white solid (1H NMR (CDCl3, 300 MHz): δ 3.59-3.40 (m, 2H), 3.36-3.05 (m, 2H), 3.02-2.76 (m, 2H), 2.65-2.60 (m, 1H), 2.24-2.04 (m, 2H), 1.85-1.66 (m, 2H), 1.46 (s, 9H); MS (m/z): 256 (M+1), 200 (M+1-56)).

1. concentrationconcentrated (12 N) hydrochloric acid (75 mL)
2. temperatureThe mixture was heated
3. temperatureat reflux for 8 h
4. customThe volatiles were evaporated
5. dissolutionthe residue was dissolved in water (10 mL)
6. extractionThe aqueous layer was extracted with ethyl acetate (200 mL)
7. washThe organic layer was washed with water (2×200 mL) and brine (100 mL)
8. dry with materialdried (anhydrous sodium sulfate)
9. concentrationconcentrated
10. custom(rotary evaporation)
11. custompurified by silica gel column chromatography

ORD record

ord-96f68b18aeaf4581944a6e168fe9be6f

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08198296B2