Synthetic method of methyl 4-chlorobutyrate

Abstract

The invention discloses a synthetic method of methyl 4-chlorobutyrate. The method comprises the following steps: adding gamma-butyrolactone, methanol and an acidic catalyst into a reactor, adding phosphorus trichloride in drops under an atmospheric pressure and a temperature of 30 to 60 DEG C, keeping warm and continuously reacting for 0.5 to 2 hours after the adding, and getting the methyl 4-chlorobutyrate through a post-treatment of the reaction solution after the reaction, wherein the acidic catalyst is 1 to 5 % by mole amount of the gamma-butyrolactone, the mole ratio of the gamma-butyrolactone and the methanol is 1 : 2-5, and the mole ratio of the gamma-butyrolactone and the phosphorus trichloride is 1 : 0.35-1. The synthetic method of the methyl 4-chlorobutyrate has characteristics of mild reaction condition, concise technology, environmentally-friendly raw materials, less three waste (waste gas, waste water and industrial residue) and simple post-treatment.

Description

technical field

[0001] The invention relates to a method for synthesizing organic compounds, in particular to a method for synthesizing 4-chlorobutyrate methyl ester (Methyl4-chlorobutyrate). Background technique

[0002] Methyl 4-chlorobutyrate (S-1) is an important intermediate in the synthesis of cyclopropylamine. Cyprofloxacin is an important intermediate and raw material for the synthesis of new quinolone antibacterial drugs ciprofloxacin, sparfloxacin, timemefloxacin and baroxacin. In addition, the herbicide 6-cyclopropylamino-2-chloro-s-triazine, cyprochlor, ciprozine, ciprozine, the antiparasitic drug N-cyclopropyl-1,3,5-triazine- The synthesis of 2,4,6-triamine and the insecticide 2-cyclopropylamino-4,6-diamino-tripyran also requires the use of cyclopropylamine as an important intermediate.

[0003]

[0004] At present, the general synthesis method of 4-chlorobutyric acid methyl ester is to use zinc chloride as a catalyst, thionyl chloride to chlorinate gamma-b...

Examples

Embodiment 1

[0022] Embodiment 1, a kind of synthetic method of methyl 4-chlorobutyrate:

[0023] Into a 250mL reactor, add 43g (0.5mol) of γ-butyrolactone, 40mL (1.5mol) of methanol, and 1.36g (0.01mol) of zinc chloride. Start stirring, and add 34.3g (0.25mol) of phosphorus trichloride dropwise at normal pressure and 50°C for 30 minutes. After dropping, keep warm and continue to react for 1 hour. The reaction solution was distilled under reduced pressure, and the fraction at 80-85° C. was collected under a pressure of 25 mm Hg to obtain 65.1 g of methyl 4-chlorobutyrate. The mass content is 99.1%, and the yield is 94.5%.

Embodiment 2

[0024] Embodiment 2, a kind of synthetic method of methyl 4-chlorobutyrate:

[0025] Into a 250mL reactor, add 43g (0.5mol) of γ-butyrolactone, 60mL (1mol) of methanol, and 1.36g (0.01mol) of zinc chloride. Start stirring, and add 34.3 g (0.25 mol) of phosphorus trichloride dropwise at normal pressure at 50°C for 30 minutes. After dropping, keep warm and continue to react for 1 hour. The reaction solution was distilled under reduced pressure, and the fraction at 80-85°C was collected under a pressure of 25 mm Hg to obtain 58.4 g of methyl 4-chlorobutyrate with a content of 99.0% and a yield of 85.5%.

Embodiment 3

[0026] Embodiment 3, a kind of synthetic method of methyl 4-chlorobutyrate:

[0027] Into a 250mL reactor, add 43g (0.5mol) of γ-butyrolactone, 100mL (2.5mol) of methanol, and 1.36g (0.01mol) of zinc chloride. Start stirring, and add 34.3 g (0.25 mol) of phosphorus trichloride dropwise at normal pressure at 50°C for 30 minutes. After dropping, keep warm and continue to react for 1 hour. The reaction solution was distilled under reduced pressure, and the fraction at 80-85°C was collected under a pressure of 25 mm Hg to obtain 63.8 g of methyl 4-chlorobutyrate with a content of 99.1% and a yield of 93.4%.

technical field

[0001] The invention relates to a method for synthesizing organic compounds, in particular to a method for synthesizing 4-chlorobutyrate methyl ester (Methyl4-chlorobutyrate). Background technique

[0002] Methyl 4-chlorobutyrate (S-1) is an important intermediate in the synthesis of cyclopropylamine. Cyprofloxacin is an important intermediate and raw material for the synthesis of new quinolone antibacterial drugs ciprofloxacin, sparfloxacin, timemefloxacin and baroxacin. In addition, the herbicide 6-cyclopropylamino-2-chloro-s-triazine, cyprochlor, ciprozine, ciprozine, the antiparasitic drug N-cyclopropyl-1,3,5-triazine- The synthesis of 2,4,6-triamine and the insecticide 2-cyclopropylamino-4,6-diamino-tripyran also requires the use of cyclopropylamine as an important intermediate.

[0003]

[0004] At present, the general synthesis method of 4-chlorobutyric acid methyl ester is to use zinc chloride as a catalyst, thionyl chloride to chlorinate gamma-b...

Examples

Embodiment 1

[0022] Embodiment 1, a kind of synthetic method of methyl 4-chlorobutyrate:

[0023] Into a 250mL reactor, add 43g (0.5mol) of γ-butyrolactone, 40mL (1.5mol) of methanol, and 1.36g (0.01mol) of zinc chloride. Start stirring, and add 34.3g (0.25mol) of phosphorus trichloride dropwise at normal pressure and 50°C for 30 minutes. After dropping, keep warm and continue to react for 1 hour. The reaction solution was distilled under reduced pressure, and the fraction at 80-85° C. was collected under a pressure of 25 mm Hg to obtain 65.1 g of methyl 4-chlorobutyrate. The mass content is 99.1%, and the yield is 94.5%.

Embodiment 2

[0024] Embodiment 2, a kind of synthetic method of methyl 4-chlorobutyrate:

[0025] Into a 250mL reactor, add 43g (0.5mol) of γ-butyrolactone, 60mL (1mol) of methanol, and 1.36g (0.01mol) of zinc chloride. Start stirring, and add 34.3 g (0.25 mol) of phosphorus trichloride dropwise at normal pressure at 50°C for 30 minutes. After dropping, keep warm and continue to react for 1 hour. The reaction solution was distilled under reduced pressure, and the fraction at 80-85°C was collected under a pressure of 25 mm Hg to obtain 58.4 g of methyl 4-chlorobutyrate with a content of 99.0% and a yield of 85.5%.

Embodiment 3

[0026] Embodiment 3, a kind of synthetic method of methyl 4-chlorobutyrate:

[0027] Into a 250mL reactor, add 43g (0.5mol) of γ-butyrolactone, 100mL (2.5mol) of methanol, and 1.36g (0.01mol) of zinc chloride. Start stirring, and add 34.3 g (0.25 mol) of phosphorus trichloride dropwise at normal pressure at 50°C for 30 minutes. After dropping, keep warm and continue to react for 1 hour. The reaction solution was distilled under reduced pressure, and the fraction at 80-85°C was collected under a pressure of 25 mm Hg to obtain 63.8 g of methyl 4-chlorobutyrate with a content of 99.1% and a yield of 93.4%.

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