Methyl 4-methoxyacetoacetate

colorless to yellow liquid

REFERENCE EXAMPLE 6 In 2L pre-reaction bottle by adding 250 ml tetrahydrofuran, under the protection of argon, are started to stir, the oven 25 °C, the inner temperature 15-25 °C added in batches under the condition of 30g (0.74mol) sodium hydride (containing 40 wt percent mineral oil) and 50g (0.74mol) potassium methoxide, continue adding tetrahydrofuran after adding 450 ml; the inner temperature 20 °C slowly dropping under the condition of 30g methanol and 100g (0.67mol) 4-chloro acetyl mixed solution of methyl acetate, regulate the stirring in the rate of 310 R/min the left and the right, about 4h finish; to temperature rise within 20-25 °C stirring 5h, TLC detection complete raw material reaction: cooling system, can be seen and the color is yellowish solution a large number of solid suspended, the inner temperature 11 °C add under the condition of 200 ml tetrahydrofuran, to be oven to -2 ° C time, slowly adding 100 ml molar concentration is 2mol/L hydrochloric acid solution (pre-cooling to 0-5 °C), keep the oven in the 0 °C the following, about 20 min after adding, pH= 10 of the reaction system at this time, in the process of dropping the solid significant increase in the reaction bottle, immediately after adding filtering, the filter cake is a white solid, cake obtained drying filters 92g solid; the resulting solid is added to the 770g in ethyl acetate, the temperature of the reaction system to 0 °C, slow instillment mole concentration is 6mol/L hydrochloric acid solution, maintaining the temperature of the reaction system is not variable, the dropping white solid gradually disappear in the process, the reaction system is adjusted pH= 4, reaction liquid contains a small amount of inorganic salt white solid, filtering the reaction solution, the filtrate layer, the organic phase is separated, the organic phase by adding 5g activated carbon, in the 30 °C under the condition of stirring 1h, filtered, filtrate in the 35 °C ethyl acetate under the condition of the vacuum distillation to the colorless liquid 74g, HPLC checking the purity of 99.6percent.In a 2 L reaction flask, 250 ml of a solvent tetrahydrofuran (AR) was added. Under argon protection, stirring was started and at this time the kettle temperature is 25°C. Was added portionwise 30 g (0.75 mol) of industrial sodium hydride (containing 40 wtpercent mineral oil) and 53 g (0.75 mol) of potassium methoxide. After the addition, continue to add solvent tetrahydrofuran 450ml; The temperature in the kettle was 20°C. Was slowly added dropwise 30 g of methanol mixed with 100 g (0.68 mol) methyl 4-chloro-3-oxo-butanoate and stirred reaction for 4h. The reactor temperature increased to 25°C and stirred for 5h. TLC detection reaction is completed. The system began to cool down. Solution color is khaki and a large number of solid suspension. When the temperature inside the kettle drops to 6°C, 2M hydrochloric acid solution (pre-cooled to 0-5 ° C) was slowly added to the system pH = 7; Standing stratification. After separation, the upper layer was concentrated to dryness to remove the solvent tetrahydrofuran. The resulting residue was added with 60 ml of ethyl acetate. After concentrating by rotary evaporation, ehyl acetate (60 ml) was added thereto. Concentrated by rotary evaporation, ethyl acetate (200 ml) was added thereto. After stirring for a while, the lower aqueous phase was extracted three times with ethyl acetate (80 ml, 60 ml, 60 ml). All organic phases were combined. Saturated sodium chloride wash (60mlx2) to pH = 7 or so. Concentrated to give a pale yellow oil, which was subjected to wiping film molecular distillation. When the degree of vacuum was 30 Pa, at a temperature of 50°C, scraper speed of 400r / min, to obtain 89 g of methyl 4-methoxyacetoacetate as a colorless oily liquid, purity was 95.4percent by HPLC.

An intermediate used in the synthesis of dotrevir sodium

Molecular Weight:146.14
XLogP3:-0.1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:5
Exact Mass:146.05790880
Monoisotopic Mass:146.05790880
Topological Polar Surface Area:52.6
Heavy Atom Count:10
Complexity:130
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes