Methanol → (1R,2S)-2-(Methoxycarbonyl)cyclohexane-1-carboxylic acid

Temperature

-55 °C

(1S,2R)-Cyclohexane-1,2-dicarboxylic acid monomethyl ester was prepared as described in J. Org. Chem. 2000, 65, 6984-6991. cis-1,2-Cyclohexanedicarboxylic anhydride (4.48 g, 29.1 mmol) was suspended in a 1:1 mixture of toluene and carbon tetrachloride (582 mL). The mixture was stirred for 20 min. Quinine (10.38 g, 32 mmol) was added and the flask was degassed and backfilled with nitrogen. The solution was cooled to −55° C. While stirring, methanol (3.55 mL, 87.3 mmol) was added dropwise. The mixture was stirred at −55° C. for 20 h. Upon warming to 25° C., the mixture was concentrated in vacuo to dryness. The resulting residue was dissolved in ethyl acetate (400 mL), washed with 3.0 M aqueous hydrochloric acid solution (2×150 mL), saturated aqueous brine solution (100 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the desired product, (1S,2R)-cyclohexane-1,2-dicarboxylic acid monomethyl ester (5.41 g, 29.1 mmol, 100%), as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ: 1.37-2.05 (8H, m), 2.84-2.86 (2H, m), 3.68 (3H, s), 11.47 (1H, s).

1. custom(1S,2R)-Cyclohexane-1,2-dicarboxylic acid monomethyl ester was prepared
2. customthe flask was degassed
3. stirringWhile stirring
4. stirringThe mixture was stirred at −55° C. for 20 h
5. temperatureUpon warming to 25° C.
6. concentrationthe mixture was concentrated in vacuo to dryness
7. dissolutionThe resulting residue was dissolved in ethyl acetate (400 mL)
8. washwashed with 3.0 M aqueous hydrochloric acid solution (2×150 mL), saturated aqueous brine solution (100 mL)
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD record

ord-63f9e3c28fa04cdcb083fe0b335d3754

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07582626B2