Tetrahydrofuran → Diethyl methyl(3-methylbut-2-en-1-yl)propanedioate

Temperature

0 °C

A solution of 2-methyl-malonic acid diethyl ester (20.0 g, 115 mmol) in tetrahydrofuran (50 mL) was added dropwise over 15 min to a suspension of sodium hydride (2.89 g, 120 mmol) in tetrahydrofuran (100 mL) at 0° C. The clear reaction mixture was stirred for 5 min at 0° C., then a solution of 1-bromo-3-methyl-but-2-ene (18.8 g, 126 mmol) in tetrahydrofuran (30 mL) was added over 10 min. The reaction mixture was allowed to warm to 25° C. and was stirred at that temperature for 22 h. After quenching with 1.0 M aqueous hydrochloric acid solution (20 mL), the mixture was partitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and ethyl acetate (2×150 mL). The organic layers were dried over sodium sulfate and were concentrated in vacuo. The residue was purified by flash chromatography (self packed glass column, gradient elution: 5-20% ethyl acetate in hexanes) to afford rac-2-methyl-2-(3-methyl-but-2-enyl)-malonic acid diethyl ester (22.15 g, 91.4 mmol, 79%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ: 1.25 (6H, t, J=7.0 Hz), 1.37 (3H, s), 1.62 (3H, s), 1.69 (3H, s), 2.57 (2H, d, J=7.0 Hz), 4.17 (4H, q, J=7.0 Hz), 4.99-5.03 (1H, m).

1. temperatureto warm to 25° C.
2. stirringwas stirred at that temperature for 22 h
3. customAfter quenching with 1.0 M aqueous hydrochloric acid solution (20 mL)
4. customthe mixture was partitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and ethyl acetate (2×150 mL)
5. dry with materialThe organic layers were dried over sodium sulfate
6. concentrationwere concentrated in vacuo
7. customThe residue was purified by flash chromatography (self packed glass column, gradient elution: 5-20% ethyl acetate in hexanes)

ORD record

ord-b65c2c9c05224a96a6d966beea8e4f04

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08222404B2