Dimethyl 1,4-cyclohexanedicarboxylate → Dimethyl 1-(2-chloroethyl)cyclohexane-1,4-dicarboxylate

Temperature

-78 °C

To the above described mixture of crude dimethyl cyclohexane-1,4-dicarboxylate (100 g, 0.5 mol) and hexamethylphosphoramide (360 mL, 2 mol) in anhydrous THF (800 mL) was added the freshly prepared lithium diisopropylamide solution (preparation described above) over 30 min at −40° C. After stirring for 1 h at this temperature, 1-bromo-2-chloroethane (42 mL, 0.5 mol) was added over 1. The mixture was stirred for 3 h at −78° C. and then stirred overnight at room temperature. The reaction was quenched by the addition of aqueous hydrochloric acid solution (3 N, 420 mL). The solvent was removed under reduced pressure. The aqueous layer was extracted with ethyl acetate (200 mL×3). The combined extracts were washed with brine (2×300 mL) and dried over sodium sulfate. Concentration gave the title compound (116 g, yield 88%) which was used in the next step without further purification; 1H NMR (400 MHz, CDCl3) δ ppm 3.72 (s, 3H), 3.65 (s. 3H), 3.46-3.42 (m, 2H), 2.33-2.21 (m, 3H), 2.05-1.85 (m, 4H), 1.58-1.42 (m, 2H), 1.25-1.15 (m, 2H).

1. additionwas added over 1
2. stirringstirred overnight at room temperature
3. customThe reaction was quenched by the addition of aqueous hydrochloric acid solution (3 N, 420 mL)
4. customThe solvent was removed under reduced pressure
5. extractionThe aqueous layer was extracted with ethyl acetate (200 mL×3)
6. washThe combined extracts were washed with brine (2×300 mL)
7. dry with materialdried over sodium sulfate
8. concentrationConcentration

ORD record

ord-56f675e93ab74dde81fce4be256d8946

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09139534B2