1-tert-Butyl 3-methyl 2-methylmalonate synthesis

Yield:132180-14-4 77%

Reaction Conditions:

Stage #1: methyl t-butyl malonatewith sodium hydride in N,N-dimethyl-formamide;mineral oil at 0; for 30 h;
Stage #2: methyl iodide in N,N-dimethyl-formamide;mineral oil at 0 - 20; for 18 h;

Steps:

4 4.4 1-tert-Butyl 3-methyl 2-methylmalonate 3

A 100 mL round-bottom flask equipped with a stirring bar was charged with compound 7 (1920 mg, 11.0 mmol) and DMF (25 mL). To the solution, sodium hydride (60% oil suspension, 446 mg, 11.0 mmol) was added. The reaction was allowed to stir at 0 °C for 30 h. To the mixture, methyl iodide (670 μL, 11.0 mmol) was added at 0 °C and the mixture was stirred at room temperature for 18 h. To the reaction mixture, H₂O was added, and the mixture was extracted with CH₂Cl₂ (3x), dried over MgSO₄, and concentrated in vacuo. The remaining residue was purified by silica gel column chromatography (hexanes/AcOEt = 90:10) to afford the desired product 3 (1597 mg, 77%) as a colorless oil. ¹H NMR (400 MHz, CDCl₃) δ 3.73 (s, 3H), 3.35 (q, J = 7.3 Hz, 1H), 1.46 (s, 9H), 1.38 (d, J = 7.3 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 170.9, 169.2, 81.6, 52.2, 47.0, 27.8, 13.5.

References:

Kanemitsu, Takuya;Furukoshi, Saeka;Miyazaki, Michiko;Nagata, Kazuhiro;Itoh, Takashi [Tetrahedron Asymmetry,2015,vol. 26,# 4,p. 214 - 218]