Methanol → 1,3-Dimethyl 1,3-cyclopentanedicarboxylate

Temperature

7 °C

A 5-L, 3-neck, round bottom flask was equipped with a mechanical stirrer, a J-KEM temperature controller, and a reflux condenser. The flask was charged with cyclopentane-1,3-dicarboxylic acid (357 g, 2.262 mol) and methanol (1.75 L). The solution was cooled to 7° C. using an ice/water bath. Concentrated sulfuric acid (70 mL) was added dropwise over 30 min resulting in an exotherm up to 12° C. The reaction mixture was heated to reflux and stirred for 16 h when TLC analysis (10% methanol/ethyl acetate) indicated that the reaction was complete. The reaction mixture was concentrated, redissolved in methyl tert-butyl ether, and washed with saturated aqueous sodium bicarbonate (2×150 mL) and brine (2×150 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting clear oil was dissolved in hexane (2 L) and treated with a 2 N aqueous sodium hydroxide solution (950 mL) until the pH˜10. The layers were separated and the aqueous layer was extracted with hexane (4×1 L). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated to provide 360 g (100%) of dimethyl cyclopentane-1,3-dicarboxylate as a clear oil. 1H NMR (500 Hz, CDCl3) δ ppm 3.67 (s, 6H), 2.75-2.83 (m, 2H), 2.20-2.26 (m, 1H), 2.05-2.12 (m, 1H), 1.90-2.0 (m, 4H).

1. customresulting in an exotherm up to 12° C
2. temperatureThe reaction mixture was heated
3. temperatureto reflux
4. concentrationThe reaction mixture was concentrated
5. dissolutionredissolved in methyl tert-butyl ether
6. washwashed with saturated aqueous sodium bicarbonate (2×150 mL) and brine (2×150 mL)
7. dry with materialThe organic layer was dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. dissolutionThe resulting clear oil was dissolved in hexane (2 L)
11. additiontreated with a 2 N aqueous sodium hydroxide solution (950 mL) until the pH˜10
12. customThe layers were separated
13. extractionthe aqueous layer was extracted with hexane (4×1 L)
14. dry with materialdried over sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated

ORD record

ord-8a7cc624c019475aa1118b2d9b41428e

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09139534B2