Preparation of P(NMeOMe)3 agent and application thereof in synthesizing N-methyl-N-methoxylamide

A technology of methoxyamide and trimethoxyphosphonamidite, which is used in the synthesis of N-methyl-N-methoxyamide intermediates and organic synthesis intermediates. The reagent is used in the synthesis of N-methyl-N- The application field in methoxyamide can solve the problems of removal, waste of raw materials, yield, expensive deoxyfluorinating agent, etc., and achieve the effect of easy post-processing, high synthesis efficiency and environmental friendliness

Inactive Publication Date: 2008-09-10
NORTHWEST NORMAL UNIVERSITY
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  • Abstract
  • Description
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Problems solved by technology

The disadvantage of this method is that the deoxidizing fluorinating agent used is relatively expensive, and the residue or by-product after the reaction is difficult to remove from the mixture, resulting in waste of raw materials and low yield

Method used

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  • Preparation of P(NMeOMe)3 agent and application thereof in synthesizing N-methyl-N-methoxylamide
  • Preparation of P(NMeOMe)3 agent and application thereof in synthesizing N-methyl-N-methoxylamide
  • Preparation of P(NMeOMe)3 agent and application thereof in synthesizing N-methyl-N-methoxylamide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Embodiment 1, the synthesis of N-methyl-N-methoxybenzamide

[0024] Step 1, P(NOMeMe) 3 Synthesis: under ice-salt bath cooling and nitrogen protection, in a 250ml three-necked flask, add Me(MeO)NH 62mmol (3.78g) and NEt 3 70mmol (20ml), in 100ml anhydrous ether mixture, slowly add PCl dropwise with stirring 3 20 mmol (2.74 g) of anhydrous ether mixture was added dropwise, and allowed to warm to room temperature naturally. The mixture was stirred overnight, heated for 4 hours the next day, lowered to room temperature and filtered to remove the ammonia salt, and the solvent was distilled off to obtain a pale yellow liquid. Under reduced pressure distillation, 2.81 g of a colorless liquid was obtained, which was the target product 3. Yield 66.7%. Its reaction formula is as follows:

[0025]

[0026] Step 2. Synthesis of N-methyl-N-methoxyamide: In a 50mL three-necked flask, compound P(NOMeMe) 3 0.211 g (1 mmol) was dissolved in 10 ml of toluene, 0.244 g (2 mmol...

Embodiment 2

[0032]Example 2. Synthesis of N-methyl-N-methoxydithiophene-2-carboxamide

[0033] Step 1. P(NOMeMe) 3 Synthesis of : the same as in Example 1.

[0034] Step 2. Synthesis of N-methyl-N-methoxyamide: In a 50mL three-necked flask, compound P(NOMeMe) 3 0.211 g (1 mmol) was dissolved in 10 ml of toluene, 0.368 g (2 mmol) of dithiophene-2-carboxylic acid was added, and the mixture was heated at 60°C for 30 minutes under a nitrogen atmosphere. After the reaction of the raw materials was detected by TLC, it was cooled to room temperature, add saturated NaHCO 3 An aqueous solution quenched the reaction. Extract with ether, MgSO 4 dry. The compound N-methyl-N-methoxydithiophene-2-carboxamide was obtained by column chromatography. The yield was 96.6%. Its reaction formula is as follows:

[0035]

[0036] Step 3. Detection of N-methyl-N-methoxy amide compounds: The N-methyl-N-methoxy amide compounds synthesized above were subjected to 1 HNMR, IR, 13 CNMR detection, the produ...

Embodiment 3

[0040] Example 3. Synthesis of N-methyl-N-methoxy-2-(N-p-methylbenzenesulfonyl) phenylacetamide

[0041] Step 1. P(NOMeMe) 3 Synthesis: same as Example 1;

[0042] Step 2. Synthesis of N-methyl-N-methoxyamide: In a 50mL three-necked flask, compound P(NOMeMe) 3 0.211 g (1 mmol) was dissolved in 10 ml of toluene, 0.67 g (2 mmol) of p-toluenesulfonic acid-protected aniline was added, and the mixture was heated at 60° C. for 30 minutes under a nitrogen atmosphere. After TLC detection, the reaction of the raw materials was completed. After cooling to room temperature, saturated NaHCO was added. 3 An aqueous solution quenched the reaction. Extract with ether, MgSO 4 dry. The target compound, N-methyl-N-methoxy-2-(N-p-methylbenzenesulfonyl)phenylacetamide, was obtained by column chromatography. The yield was 94.7%. Its reaction formula is as follows:

[0043]

[0044] Step 3. Detection of N-methyl-N-methoxy amide compounds: The N-methyl-N-methoxy amide compounds synthesiz...

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Abstract

The invention discloses a method for synthesizing an intermediate of N-methyl-N-methoxy amide compounds, namely the N, N', N''-trimethyl- N, N', N''-trimethoxy phosphinidene amide(P(NMeOMe)3) reagent, wherein by taking the ether as a solvent and the tri-hexylamine(NEt3) as a catalyst, the phosphorus trichloride(PCl3) reacts with the N-methyl-N-methoxy amine(Me(MeO)NH), generating the reagent. When the P(NMeOMe)3 reagent of the invention is used to synthesize the N-methyl-N-methoxy amide compounds, the benzene or methylbenzene is used as a solvent, and the P(NOMeMe) 3 directly reacts with chiral or non-chiral carboxylic acids, and all types of N-methyl-N-methoxy amide compounds are obtained after processes of filtering, drying and separation. Because the P(NMeOMe)3 is used to synthesize the N-methyl-N-methoxy amide in the invention, the method of the invention has the advantages of simple process, easy collection of materials, mild reaction condition, friendly environment, high synthesized efficiency(the reaction can finish in 30 minutes at a temperature of 60 DEG C. ), high yield( between 89 to 96 percent) and easy after-treatment, and is applied to all types of acids.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and relates to an organic synthesis intermediate, in particular to an intermediate for synthesizing N-methyl-N-methoxyamide-N,N',N"-trimethyl-N, N',N"-Trimethoxyphosphonamid P(NMeOMe) 3 The preparation of this reagent also relates to the application of the reagent in the synthesis of N-methyl-N-methoxyamide. Background technique [0002] N-methyl-N-methoxyamide is a kind of very important acylation reagent, which has been widely used in the synthesis of natural products and biologically active substances. Such amides, unlike other amides, form ketones rather than alcohols when reacted with organometallic reagents such as Grignard's reagent. N-methyl-N-methoxyamides are also readily reduced to aldehydes by metal hydrides. It is worth emphasizing that when the optically active N-methyl-N-methoxyamide reacts with metal organic reagents or metal hydrides, its configuration does not change. Since ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/06C07C291/02
Inventor 胡雨来牛腾徐长明王海峰李贵花黄丹凤
Owner NORTHWEST NORMAL UNIVERSITY
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