Sodium Chloride → HCID 54197900, compound

Temperature

-78 °C

4-Bromopyridine hydrochloride (10.05 g, 51.8 mmol) was treated with potassium carbonate (7.15 g, 51.8 mmol) in water (50 mL), and the resulting solution was saturated with sodium chloride. The 4-bromopyridine free base was extracted with diethyl ether, and the solution was stored under N2 over 3 angstrom molecular sieves for 1 h. The 4-bromopyridine solution was slowly transferred by cannula to a stirred solution of 2.5 M butyllithium in hexane (21.2 mmL, 53 mmol) in anhydrous diethyl ether (100 mL), maintained at −78° C. under N2. The reaction mixture was stirred for 30 min., and then a solution of cis-1,2-cyclohexanedicarboxylic anhydride (8.33 g, 54 mmol) in anhydrous tetrahydrofuran (150 mL) was added by cannula. The reaction mixture was stirred at −78° C. for 1 h and then allowed to warm to 20° C. The reaction mixture was quenched by addition of water (200 mL), and the aqueous layer was separated and acidified to pH=4 by addition of 6 M hydrochloric acid. The aqueous layer was saturated with sodium chloride and extracted with a (1:1) mixture of ethyl acetate and tetrahydrofuran (400 mL). The organic layer was washed with sat. NaCl, dried over MgSO4, filtered, and evaporated to give cis-2-(4-pyridylcarbonyl)cyclohexanecarboxylic acid, as a solid, which was used immediately in the next step.

1. extractionThe 4-bromopyridine free base was extracted with diethyl ether
2. stirringThe reaction mixture was stirred at −78° C. for 1 h
3. temperatureto warm to 20° C
4. customThe reaction mixture was quenched by addition of water (200 mL)
5. customthe aqueous layer was separated
6. additionacidified to pH=4 by addition of 6 M hydrochloric acid
7. extractionextracted with a (1:1) mixture of ethyl acetate and tetrahydrofuran (400 mL)
8. washThe organic layer was washed with sat. NaCl
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. customevaporated

ORD record

ord-e5384905b8dd48f9bc1d18e2c9a49261

Source dataset

uspto-grants-2003_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06545160B2