Preparation method of 3-acetyl aminophthalimide

A technology based on phthalimide and nitrophthalic acid, which is applied in the field of preparation of pharmaceutical and chemical intermediates, can solve the problems of long reaction route, high production cost and low yield, and achieve short reaction route, The effect of low cost and high yield

Inactive Publication Date: 2016-02-17
DONGHUA UNIV
View PDF3 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In summary, the above-mentioned method has the disadvantages of long reaction route, low yield and high production cost, and the cost is relatively high in large-scale production.

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
  • Preparation method of 3-acetyl aminophthalimide
  • Preparation method of 3-acetyl aminophthalimide
  • Preparation method of 3-acetyl aminophthalimide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Add 40.8g (0.19mol) of 3-nitrophthalic acid and 250mL of 3M sodium hydroxide solution into a 1000mL three-necked flask, heat and stir until the reaction liquid becomes clear at 70°C; add 3.2g (12mmol) of Crystal water, 4.0 g of ferric chloride and activated carbon, stirred for 15 min; finally, 26 mL (0.53 mol) of 85% hydrazine hydrate was added dropwise, and the addition was completed in 30 min. The reaction was tracked by TLC and reacted for 6 h to obtain 3-aminophthalic acid. After the reaction was completed, it was filtered with suction, and the filtrate was adjusted to pH=3 by adding 4N hydrochloric acid, and a large amount of solids were precipitated. Stir at room temperature for 10 min, filter with suction, wash the solid with water, and recrystallize from ethanol to obtain 28.1 g of a yellow-white solid with a yield of 80.1%. mp: 172-174°C. IR (KBr): 3430, 1715, 1634, 1527cm -1 ; 1 HNMR (400MHz, DMSO-d 6 ): 6.68(d, J=7.3Hz, 1H), 6.84(d, J=8.3Hz, 1H), 7.05~7.2...

Embodiment 2

[0036]Add 28.0 g (0.15 mol) of 3-aminophthalic acid obtained in Example 1 into a 250 mL one-necked flask, then add 100 mL of acetic anhydride, and heat to reflux. The reaction was tracked by TLC, and the reaction was carried out for 4 hours to obtain 3-acetamidophthalic anhydride. After the reaction was completed, the reaction bottle was placed in an ice-water bath and stirred for 15 minutes, and a solid precipitated out; added diethyl ether to stir, suction filtered and washed with diethyl ether to obtain a light yellow flaky solid, which was weighed after drying to obtain 24.9 g, with a yield of 78.5%. . mp: 180-182°C. IR (KBr): 3351, 1841; 1766; 1700; 1603cm -1 . 1 HNMR (400MHz, CDCl 3 ):2.34(s,3H),7.69(d,J=7.3Hz,1H),7.82~7.93(m,1H),8.97(d,J=8.5Hz,1H),9.12(s,1H).MS (EI):205[M + ].

Embodiment 3

[0038] 24.9 g (0.12 mol) of 3-acetamidophthalic anhydride obtained in Example 2 and 15.0 g (0.25 mol) of urea were respectively added to a 250 mL round bottom flask, and DMF 100 mL was added. Heated to 100°C, followed by TLC for 6 hours to obtain 3-acetamidophthalimide. After the reaction was completed, cool to room temperature, add 100 mL of water, stir for 15 min, and a solid precipitated; suction filtered, washed the solid with water, and recrystallized with 95% ethanol to obtain 2.1 g of a yellow-white solid with a yield of 85%. mp: 238~240℃. IR (KBr): 3301, 1762, 1690, 1609, 1523, 1296cm -1 ; 1 HNMR (400MHz, DMSO-d 6 ):δ2.19(s,3H),7.50(d,J=7.3Hz,1H),7.76(t,J=7.8Hz,1H),8.46(d,J=8.4Hz,1H),9.68(s ,1H),11.42(s,1H); 13 CNMR (101MHz, DMSO-d 6 ): δ24.77, 118.11, 118.29, 125.64, 133.27, 136.10, 136.90, 169.14, 169.64, 170.68. MS(EI): 204[M + ],like figure 2 and image 3 shown.

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 preparation method of 3-acetyl aminophthalimide, comprising the following steps: dissolving 3-nitro phthalic acid in sodium hydroxide aqueous solution, then adding a reducer and a catalyst, heating to 70 to 80 DEG C, stirring and reacting for 1 to 20 hours, and recrystallizing to obtain 3-amino phthalic acid; stirring with acetic anhydride and performing reflux reaction for 1 to 10 hours to obtain N-(1,3-Dioxo-1,3-dihydro-2-benzofuran-4-yl)acetamide; dissolving the N-(1,3-Dioxo-1,3-dihydro-2-benzofuran-4-yl)acetamide in an organic solvent, adding an amino donor, and stirring and refluxing for 1 to 10 hours, thus obtaining the 3-acetyl aminophthalimide. The method is simple in operation, high in yield, short in reaction route, less in the three wastes (waste gas industrial residue), and easy for industrial production.

Description

technical field [0001] The invention belongs to the field of preparation of pharmaceutical and chemical intermediates, in particular to a preparation method of 3-acetamidophthalimide. Background technique [0002] 3-Acetamidophthalimide (1) is an important intermediate in organic synthesis and pharmaceutical synthesis. For example, this compound was developed by Celgene Biotechnology Company of the United States and was approved by FDA on March 21, 2014. It is one of the intermediates of a phosphodiesterase inhibitor Apremilast (Apremilast) oral drug for the treatment of psoriatic arthritis, and it is also an important intermediate for the synthesis of dyes (Ruchelman, A.L.; Connolly, T.J. Enantioselectivesynthesistheapremilastaminosulfoneusingcatalyticasymmetrichydrogenation.Tetrahedron : Asymmetry, 2015, 26 (10-11): 553-559. Szadowski, J. Physicochemical and dyeing properties of pigments containing 3-or4-amniophthalimide residue. Dyes and Pigments, 1981, 2 (3): 249-258.). ...

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): C07D209/48
CPCC07D209/48
Inventor 赵圣印黄强
Owner DONGHUA UNIV
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