Methyl iodide → (1s,4s)-4-(Methoxycarbonyl)-4-methylcyclohexane-1-carboxylic acid

Temperature

-78 °C

N,N-Diisopropylamine (1.18 mL, 8.35 mmol) was added dropwise to a 2M solution of nbutyllithium (4.18 mL, 8.4 mmol) at −78° C. under nitrogen. After 15 min at this temperature the solution was raised to and held at 0° C. for 15 min prior to re-cooling to −78° C. and treatment with a solution of 4-(methoxycarbonyl)cyclohexanecarboxylic acid (0.62 g, 3.34 mmol) in THF (8 mL). After 30 min., iodomethane (0.31 mL, 5 mmol) was added dropwise and the mixture was allowed to warm to rt over 2 hr. The mixture was cooled to at 0° C., quenched with 2 N HCl (10 mL) then was extracted with EtOAc (2×10 mL), washed with brine (3×15 mL), and dried over anhydrous magnesium sulfate. Concentration of the combined organic extracts afforded a yellow solid. NMR(CDCl3) consistent with crude, desired product.

1. temperatureAfter 15 min at this temperature the solution was raised to and
2. waitAfter 30 min.
3. temperatureto warm to rt over 2 hr
4. temperatureThe mixture was cooled to at 0° C.
5. customquenched with 2 N HCl (10 mL)
6. extractionthen was extracted with EtOAc (2×10 mL)
7. washwashed with brine (3×15 mL)
8. dry with materialdried over anhydrous magnesium sulfate
9. customConcentration of the combined organic extracts afforded a yellow solid

ORD record

ord-c474023607ee48d88674440f7a6c2319

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08314111B2