Hydrochloric Acid → t-Butyl 3-(1-carboxycyclopentyl)propanoate

To a stirred solution of lithium diisopropylamide (0.43 mole) in dry tetrahydrofuran (300 ml) at -20° C. under nitrogen atmosphere was added cyclopentane carboxylic acid (22.7 g; 0.20 mole). The solution was allowed to warm to room temperature and after 2 hours was cooled to -10° C. and added by cannula to a stirred solution of t-butyl 3-bromopropionate (44.4 g, 0.21 mole) in tetrahydrofuran (100 ml). The resulting solution was allowed to warm to room temperature and kept overnight. Hydrochloric acid (3N, 250 ml) was cautiously added, followed by diethyl ether (500 ml) and the layers allowed to separate. The aqueous layer was washed with diethyl ether (300 ml) and the ether layers were combined, washed with water (300 ml), dried over magnesium sulphate and evaporated to give an oil. The oil was taken up in diethyl ether (300 ml) and washed with saturated sodium hydrogen carbonate solution (3×100 ml) until no further cyclopentane carboxylic acid remained. The diethyl ether solution was then extracted with 10% sodium carbonate solution, (4×150 ml), the aqueous phase separated, acidified with 2N hydrochloric acid, and extracted with diethyl ether (3×200 ml). The diethyl ether layer was separated, washed with water (300 ml), dried over magnesium sulphate and evaporated to give an oil that readily crystallised. Recrystallisation from pentane gave a colourless solid (10.4 g, 21%) m.p. 78°-81° C. (from pentane). Found: C,64.70;; H,9.18. C13H22O4 requires: C,64.44; H,9.15%.

1. temperaturewas cooled to -10° C.
2. temperatureto warm to room temperature
3. customto separate
4. washThe aqueous layer was washed with diethyl ether (300 ml)
5. washwashed with water (300 ml)
6. dry with materialdried over magnesium sulphate
7. customevaporated
8. customto give an oil
9. washwashed with saturated sodium hydrogen carbonate solution (3×100 ml) until no further cyclopentane carboxylic acid
10. extractionThe diethyl ether solution was then extracted with 10% sodium carbonate solution, (4×150 ml), the aqueous phase
11. customseparated
12. extractionextracted with diethyl ether (3×200 ml)
13. customThe diethyl ether layer was separated
14. washwashed with water (300 ml)
15. dry with materialdried over magnesium sulphate
16. customevaporated
17. customto give an oil
18. customthat readily crystallised
19. customRecrystallisation from pentane

ORD record

ord-12154946b2cc43b2aed0754c7de242ce

Source dataset

uspto-grants-1991_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05030654