Iodine → HCID 40793572, compound

Temperature

-78 °C

A dry three-neck, round-bottom flask, equipped with a reflux condenser, was charged with magnesium turnings (1.89 g, 78 mmol) and iodine (0.131 g, 0.518 mmol). The apparatus was capped tightly with septa and purged with N2, and then anhydrous diethyl ether (80 mL) was added by cannula. The reaction mixture was stirred for 2 h, during which time the iodine was consumed. The flask was cooled with an ice bath, and then 1-bromo-3,5-difluorobenzene (10 g, 51.8 mmol) was injected in portions with stirring. The ice bath was removed, and the reaction mixture was stirred for 1 h, during which time an exotherm was evident, and much of the Mg was consumed. The supernatant solution of the Grignard reagent was slowly transferred by cannula to a stirred solution of cis-1,2-cyclohexanedicarboxylic anhydride (7.98 g, 51.8 mmol) in anhydrous ether (120 mL), maintained at −78° C. under N2. The resulting solution was stirred at −78° C. for 1 h, and then allowed to warm to 20° C. over 18 h. The reaction mixture was poured into 1M sulfuric acid (150 mL) and extracted with 200 mL hexanes. The organic layer was washed with sat. NaCl, dried over MgSO4, filtered, and evaporated to give cis-2-(3,5-difluorophenylcarbonyl)-cyclohexanecarboxylic acid, as an oil, which was used immediately in the next step.

1. customA dry three-neck, round-bottom flask, equipped with a reflux condenser
2. customThe apparatus was capped tightly with septa
3. custompurged with N2
4. additionanhydrous diethyl ether (80 mL) was added by cannula
5. customwas consumed
6. temperatureThe flask was cooled with an ice bath
7. stirringwith stirring
8. customThe ice bath was removed
9. stirringthe reaction mixture was stirred for 1 h, during which time an exotherm
10. custommuch of the Mg was consumed
11. stirringThe resulting solution was stirred at −78° C. for 1 h
12. temperatureto warm to 20° C. over 18 h
13. extractionextracted with 200 mL hexanes
14. washThe organic layer was washed with sat. NaCl
15. dry with materialdried over MgSO4
16. filtrationfiltered
17. customevaporated

ORD record

ord-1fbcc252f9bb45cf9bd8aa473e72cf0f

Source dataset

uspto-grants-2003_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06545160B2