Methyl iodide → 1-Methylcycloheptane-1-carboxylic acid

Temperature

-78 °C

To a stirred solution of diisopropylamine (7.47 g, 73.8 mmol) in dry THF at -78° C. under nitrogen was added n-butyllithium(2.5M, 29.5 ml, 73 8 mmol). The mixture was stirred for 10 minutes before cycloheptanecarboxylic acid (2.10 g, 14.8 mmol) was added dropwise and the reaction stirred at -78° C. for a further 10 minutes before refluxing for a further 2 hours. The reaction was cooled to 0° C. and methyl iodide (5.76 g, 40.6 ml) was added dropwise before refluxing for a further 1 hour before cooling to room temperature. The reaction mixture was poured onto an admixture of water/ether (100 ml/SO ml) and the aqueous layer was separated, acidified with dilute hydrochloric acid (2M) and extracted with ether (5×25 ml). The combined ether layers were washed with water (2×50 ml) and saturated sodium chloride solution (50 ml) before being dried over MgSO4. Filtration and evaporation of solvent under reduced pressure yielded the 1-methylcycloheptanecarboxylic acid which was recrystallised from hexane (2.20 g, mp 46° C.). The title compound was produced by the method of Example 24 using this acid in place of the 1-methylcyclopentanecarboxylic acid.

1. additionwas added dropwise
2. temperaturebefore refluxing for a further 2 hours
3. temperatureThe reaction was cooled to 0° C.
4. temperaturebefore refluxing for a further 1 hour
5. temperaturebefore cooling to room temperature
6. customthe aqueous layer was separated
7. extractionextracted with ether (5×25 ml)
8. washThe combined ether layers were washed with water (2×50 ml) and saturated sodium chloride solution (50 ml)
9. dry with materialbefore being dried over MgSO4
10. filtrationFiltration and evaporation of solvent under reduced pressure

ORD record

ord-7fc9f18d4dfa4c27a9d9ee6db3e35571

Source dataset

uspto-grants-1999_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05962002