Lithium hydroxide, monohydrate → (1R,3S)-3-(4-(4-chlorophenyl)piperazin-1-yl)cyclopentanecarboxylic acid

To a stirred solution of (1R,3S)-methyl 3-(4-(4-chlorophenyl)piperazin-1-yl)cyclopentanecarboxylate (1.5 g, 4.65 mmol) in tetrahudrofuran:water (4:1) was added a solution of lithium hydroxide monohydrate (0.58 g, 13.94 mmol) in 5 ml water. Reaction mixture was allowed to stir at room temperature for 20 h. Upon completion, the reaction mixture was concentrated under reduced pressure to remove tetrahudrofuran. The resulting residue was diluted with 10 ml of water followed by washing with diethyl ether (3×20 ml). The aqueous layer was acidified at 0° C. with 1N hydrochloric acid to pH 6-7 and the mixture was extracted with ethyl acetate (2×50 ml). The organic layer was separated and dried over sodium sulphate and concentrated under reduced pressure to obtain (1R,3S)-3-(4-(4-chlorophenyl)piperazin-1-yl)cyclopentanecarboxylic acid (1.0 g, 69.7%).

1. customReaction mixture
2. concentrationUpon completion, the reaction mixture was concentrated under reduced pressure
3. customto remove tetrahudrofuran
4. additionThe resulting residue was diluted with 10 ml of water
5. washby washing with diethyl ether (3×20 ml)
6. customwas acidified at 0° C. with 1N hydrochloric acid to pH 6-7
7. extractionthe mixture was extracted with ethyl acetate (2×50 ml)
8. customThe organic layer was separated
9. dry with materialdried over sodium sulphate
10. concentrationconcentrated under reduced pressure

ORD record

ord-f56ed55a87434aa0a617e3ec80191055

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09359367B2