New method for synthesizing 3-cyclopropyl methoxy-4-(difluoromethoxy) benzoic acid

A technology of difluoromethoxybenzoic acid and cyclopropylmethoxy, which is applied in the preparation of carboxylate/lactone, organic chemistry, etc., can solve problems such as difficult industrial scale-up production, and achieve easy operation and low side reaction little effect

Inactive Publication Date: 2011-06-15
NANJING SIMCERE MEDICAL LAB CO LTD +1
View PDF6 Cites 28 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Difficult to carry out ind

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • New method for synthesizing 3-cyclopropyl methoxy-4-(difluoromethoxy) benzoic acid
  • New method for synthesizing 3-cyclopropyl methoxy-4-(difluoromethoxy) benzoic acid
  • New method for synthesizing 3-cyclopropyl methoxy-4-(difluoromethoxy) benzoic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1: 3-cyclopropylmethoxy-4-difluoromethoxybenzoic acid

[0036] Step (1): Preparation of 3-nitro-4-difluoromethoxybenzoic acid methyl ester

[0037] 26.0g of methyl 3-nitro-4-hydroxybenzoate, 0.67g of benzyltrimethylammonium chloride, 31.4g of 50% sodium hydroxide and 200mL of dioxane were added to the reactor, and the Under stirring, chlorodifluoromethane was introduced into the system. After the reaction, ice water was added, extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain 28.4 g of methyl 3-nitro-4-difluoromethoxybenzoate with a yield of 87 %.

[0038] Step (2): Preparation of 3-amino-4-difluoromethoxybenzoic acid methyl ester

[0039] 28.0 g of methyl 3-nitro-4-difluoromethoxybenzoate was dissolved in 500 mL of methanol, 2.8 g of 10% palladium carbon (containing 50% water) was added, and hydrogenated at normal pressure for 10 h. Palladium carbon was removed by filtration...

Embodiment 2

[0045] Example 2: 3-cyclopropylmethoxy-4-difluoromethoxybenzoic acid

[0046] Step (1): Preparation of ethyl 3-nitro-4-difluoromethoxybenzoate

[0047] Add 35.0g of ethyl 3-nitro-4-hydroxybenzoate, 3.5g of tetrabutylammonium bromide, 65mL of 35% sodium hydroxide and 250mL of toluene into the reactor. into chlorodifluoromethane. After the reaction, ice water was added, the organic phase was separated, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain 36.8 g of ethyl 3-nitro-4-difluoromethoxybenzoate with a yield of 85%. .

[0048] Step (2): Preparation of ethyl 3-amino-4-difluoromethoxybenzoate

[0049] 36.0 g of ethyl 3-nitro-4-difluoromethoxybenzoate was dissolved in 500 mL of glacial acetic acid, 63.0 g of iron powder was added in batches at room temperature, and stirred for another 3 h. Add 500mL of toluene, filter through celite, and concentrate the filtrate. The residue was dissolved in ethyl acetate, washed with ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to a new method for synthesizing 3-cyclopropyl methoxy-4-(difluoromethoxy) benzoic acid. The method is characterized by taking 3-nitro-4-hydroxybenzoic acid ester as the raw material to obtain the 3-cyclopropyl methoxy-4-(difluoromethoxy) benzoic acid through alkylation, reduction, diazotization, hydrolysis, alkylation, deprotection and the like. The 3-cyclopropyl methoxy-4-(difluoromethoxy) benzoic acid is a key intermediate for synthesizing the drug roflumilast.

Description

technical field [0001] The present invention relates to a new method for synthesizing 3-cyclopropylmethoxy-4-difluoromethoxybenzoic acid, 3-cyclopropylmethoxy-4-difluoromethoxybenzoic acid is a synthetic drug The key intermediate of roflumilast. Background technique [0002] Roflumilast (Daxas) was jointly developed by Swiss Nycomed Company and American Forest Company, and was approved for marketing by the European Union on July 6, 2010, for the treatment of chronic obstructive pulmonary disease (COPD). Roflumilast is a selective phosphodiesterase 4 (PDE4) inhibitor, which is a new class of COPD treatment drug approved by the European Union for the first time in more than ten years. Roflumilast is a once-a-day oral tablet that must be used in combination with other bronchodilators for the treatment of chronic bronchitis-associated severe COPD (diastolic FEV1 less than 50% of predicted value) in adult patients with a history of frequent exacerbations Maintenance treatment. ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07C51/09C07C65/26
Inventor 廖明毅李瑞杨少宁张连第丁磊
Owner NANJING SIMCERE MEDICAL LAB CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap