Methyl iodide → Diethyl 2-Isopentyl-2-methylmalonate

Temperature

25 °C

A solution of diethyl isopentylmalonate (2.31 g, 10 mmol) in a 6:2 mixture of anhydrous N,N-dimethylformamide/diethyl ether (8 mL) was stirred under a nitrogen atmosphere at 25° C. and treated with a 60% oil dispersion of sodium hydride (480 mg, 12 mmol). The reaction mixture was stirred until the evolution of hydrogen gas ceased. The reaction was then treated dropwise via syringe with iodomethane (1.87 mL, 30 mmol) and stirred for 3 h at 25° C. The reaction was quenched with a 1.0 M aqueous hydrochloric acid solution (30 mL) and extracted with diethyl ether (2×50 mL). The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (50 mL) and saturated aqueous brine solution (50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to afford the desired product, 2-methyl-2-(3-methyl-butyl)-malonic acid diethyl ester (2.09 g, 8.56 mmol, 85%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 0.88 (d, 6H, J=6.9 Hz), 1.06-1.12 (m, 2H), 1.24 (t, 6H, J=7.0 Hz), 1.38 (s, 3H), 1.51 (septet, 1H, J=6.6 Hz), 1.82-1.87 (m, 2H), 4.12-4.20 (m, 4H). LC-MS (ESI) calculated for C13H24O4 244.17. found 245.3 [M+H+].

1. stirringstirred for 3 h at 25° C
2. customThe reaction was quenched with a 1.0 M aqueous hydrochloric acid solution (30 mL)
3. extractionextracted with diethyl ether (2×50 mL)
4. washThe combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (50 mL) and saturated aqueous brine solution (50 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORD record

ord-78074356e17a4544a50d749ae8b043c7

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08097613B2