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Production method of N, O-bis (trimethylsilyl) acetamide

A technology of silyl acetamide and trimethylsilyl imidazole, which is applied in the production field of N,O-bistrimethylsilyl acetamide, can solve the problems of low reactivity, affecting product quality and yield, and achieve high yield high effect

Active Publication Date: 2022-07-15
泽升科技(广州)有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among these silylating reagents, the advantages of acidic and alkaline silylating reagents are that they are cheap and easy to obtain, but the disadvantages are low reactivity and the need to remove by-products formed in the reaction, thus affecting the quality and yield of products

Method used

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  • Production method of N, O-bis (trimethylsilyl) acetamide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] A preparation method of N,O-bistrimethylsilylacetamide,

[0039] Preparation of sulfhydryl compounds: 2-amino-4-nitrophenol, tetramethylthiuram disulfide, and alkaline reagents were added to the solvent, reacted at 120° C. for 4 hours, and separated by silica gel column to obtain sulfhydryl compounds. Solvent is DMF, the usage amount of 2-amino-4-nitrophenol is 3wt% of DMF, and the usage mole amount of tetramethylthiuram disulfide is 100% of the usage mole amount of 2-amino-4-nitrophenol %, the basic reagent is potassium carbonate, and the used molar amount of the basic reagent is 300% of the used molar amount of 2-amino-4-nitrophenol.

[0040] Sulfhydryl compound in 78% yield. 1 H NMR (400 MHz, DMSO-d 6 , TMS): δ(ppm) 8.12 (d, J = 8.0 Hz, 1H), 7.86 (s, 1H), 7.69 (d, J = 8.0 Hz, 1H).HRMS (ESI): Calcd forC 7 H 4 N 2 O 3 S (195.9943), found: 195.9973.

[0041] Preparation of N,O-bistrimethylsilylacetamide: Mix trimethylsilyl imidazole and mercapto compound to obtain ...

Embodiment 2

[0043] A preparation method of N,O-bistrimethylsilylacetamide,

[0044] Preparation of sulfhydryl compounds: 2-amino-4-nitrophenol, tetramethylthiuram disulfide, and alkaline reagents were added to the solvent, reacted at 120° C. for 4 hours, and separated by silica gel column to obtain sulfhydryl compounds. Solvent is DMF, the usage amount of 2-amino-4-nitrophenol is 3wt% of DMF, and the usage mole amount of tetramethylthiuram disulfide is 100% of the usage mole amount of 2-amino-4-nitrophenol %, the basic reagent is potassium carbonate, and the used molar amount of the basic reagent is 300% of the used molar amount of 2-amino-4-nitrophenol.

[0045] Preparation of N,O-bistrimethylsilylacetamide: mix trimethylsilyl imidazole and mercapto compound to obtain trimethylsilyl imidazole-mercapto compound solution, then dropwise add acetamide-trimethyl chlorosilane solution, in The reaction was stirred at a temperature of 160 °C for 5 h, the reaction pressure was controlled to a va...

Embodiment 3

[0047] A preparation method of N,O-bistrimethylsilylacetamide,

[0048] Preparation of sulfhydryl compounds: 2-amino-4-nitrophenol, tetramethylthiuram disulfide, and alkaline reagents were added to the solvent, reacted at 120° C. for 4 hours, and separated by silica gel column to obtain sulfhydryl compounds. Solvent is DMF, the usage amount of 2-amino-4-nitrophenol is 3wt% of DMF, and the usage mole amount of tetramethylthiuram disulfide is 100% of the usage mole amount of 2-amino-4-nitrophenol %, the basic reagent is potassium carbonate, and the used molar amount of the basic reagent is 300% of the used molar amount of 2-amino-4-nitrophenol.

[0049] Preparation of N,O-bistrimethylsilylacetamide: Mix trimethylsilyl imidazole, N-trimethylsilyl acetamide and mercapto compound to obtain a trimethylsilyl imidazole-mercapto compound solution, and then dropwise add ethyl acetate The amide-trimethylsilyl imidazole solution was stirred and reacted at a temperature of 160 °C for 5 h,...

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Abstract

The invention discloses a production method of N, O-bis (trimethylsilyl) acetamide, belongs to the technical field of production of medical intermediates, and particularly relates to a method for obtaining a sulfhydryl compound by reacting 2-amino-4-nitrophenol with tetramethylthiuram disulfide under the action of an alkaline reagent; the preparation method comprises the following steps: mixing a trimethylsilyl imidazole-sulfhydryl compound solution with an acetamide-trimethylsilyl imidazole solution, and reacting to prepare N, O-bis (trimethylsilyl) acetamide; the trimethylsilyl imidazole-sulfhydryl compound solution at least contains trimethylsilyl imidazole and a sulfhydryl compound; the acetamide-trimethylsilyl imidazole solution is formed by mixing acetamide and trimethylsilyl imidazole. The yield of the N, O-bis (trimethylsilyl) acetamide prepared by the method disclosed by the invention is 80 to 90 percent.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical intermediate production, in particular to a production method of N,O-bistrimethylsilylacetamide. Background technique [0002] Bis(trimethylsilyl)acetamide, referred to as BSA, is an important pharmaceutical intermediate. It is mainly used as a neutral silylation reagent in the silylation protection of amino acids, carboxylic acids, alcohols and amides, especially in cephalosporins. It is widely used in the synthesis of antibiotics. Cephalosporin antibiotics are the most rapidly developed, the most variety and the fastest type of antibiotics in foreign countries since the 1970s. Because of its broad antibacterial spectrum, strong bactericidal power, high stability to β-lactamase, lower toxicity and side effects than semi-synthetic penicillin, and good clinical efficacy, it still ranks first in all kinds of antibiotics in the domestic and foreign drug markets. In the synthesis of cephalosp...

Claims

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Application Information

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IPC IPC(8): C07F7/18C07F7/20
CPCC07F7/1896C07F7/20Y02P20/55
Inventor 罗波许峰宋保风
Owner 泽升科技(广州)有限公司