Synthesis
NaH (7.71 g, 192.7 mmol) was suspended in DMF (110 mL) and cooled to 0°C in an ice bath. A solution of MeOH (2.64 g, 82.5 mmol) in DMF (55 mL) was slowly added dropwise. After the dropwise addition, stirring was continued for 30 min at 0 °C. Subsequently, a DMF (55 mL) solution of ethyl 4-chloroacetoacetate (9.54 g, 57.9 mmol) was added slowly dropwise at 0 °C. After completion of the dropwise addition, the reaction mixture was slowly warmed to room temperature and stirred for 16 hours. After completion of the reaction, the reaction mixture was diluted with 1N HCl (400 mL) and extracted with MTBE (250 mL x 3). The organic phases were combined, washed with H2O (200 mL × 5), dried over anhydrous Na2SO4, filtered and concentrated. Finally, it was purified by silica gel column chromatography (eluent ratio PE:EA = 10:1) to afford ethyl 4-methoxy-3-oxobutanoate (1.4 g, 15.1% yield) as a light yellow oil.
References
[1] Patent: JP2015/214548, 2015, A. Location in patent: Paragraph 0992; 0993
[2] Patent: CN105481694, 2016, A. Location in patent: Paragraph 0015; 0016; 0017; 0018; 0019; 0020; 0021 - 0023
