Unlock instant, AI-driven research and patent intelligence for your innovation.

A kind of preparation method of 3-oxetane carboxylic acid

A technology of oxetane carboxylic acid and oxidation reaction, which is applied in the field of pharmaceutical intermediates and synthesis, and can solve the problems of unpublished 3-oxetanone synthesis method, unfavorable large-scale production and preparation, and high requirements for production process conditions , achieve important market value, facilitate industrial production, and shorten the effect of reaction steps

Active Publication Date: 2019-06-14
SHANGHAI BALMXY PHARMA CO LTD
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, in this route, the reaction steps are cumbersome, requiring ten steps of reaction, the total yield is very low, less than 50%, and most of the key steps require column chromatography purification, which is not suitable for industrial scale-up
[0005] At present, only CN106565637A discloses a kind of synthetic method of 3 oxetane acetic acid, and this synthetic method comprises step 1, 3 oxetanone and (benzyloxycarbonyl methylene) triphenylphosphine react to obtain intermediate product 2 (oxetane 3 base methylene) benzyl acetate; step 2, the intermediate product 2 (oxetane 3 base methylene) benzyl acetate hydrogenation debenzylation to obtain the final product 3 oxetane Butaneacetic acid, although the target product is similar to 3-oxetane carboxylic acid in this method, it is different in essence, and this method does not disclose the synthetic method and production process of the key raw material 3-oxetane ketone The condition requirements are high, which is not conducive to large-scale production and preparation

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
  • A kind of preparation method of 3-oxetane carboxylic acid
  • A kind of preparation method of 3-oxetane carboxylic acid
  • A kind of preparation method of 3-oxetane carboxylic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] This embodiment prepares 3-oxetane carboxylic acid through the following steps

[0068] (1) The compound shown in formula I is prepared by 2-hydroxymethyl-2-nitro-1,3-propanediol, and the specific reaction formula is as follows:

[0069]

[0070] 2-Hydroxymethyl-2-nitro-1,3-propanediol (302g, 2mol) was added to dichloroethane (4L), triethylamine (1.1L) was added, stirred, toluyl chloride (984g, 7mol), stirred, and the system was heated to 60°C for 10h. Wash three times with water, three times with 0.5M hydrochloric acid, three times with saturated brine, dry and concentrate. The residue was recrystallized from ethanol to obtain 871 g of white powder with a yield of 94%.

[0071] 1 H NMR (CDCl 3 ,400MHz): δ7.95-7.28(m,15H),4.85(s 6H).

[0072] (2) prepare the compound shown in formula II by the compound shown in formula I, concrete reaction formula is as follows:

[0073]

[0074] Add the white powder (700g, 1.51mol) obtained in step (1) to a 10L reaction fla...

Embodiment 2

[0089] This embodiment prepares 3-oxetane carboxylic acid through the following steps

[0090] (1) The compound shown in formula I is prepared by 2-hydroxymethyl-2-nitro-1,3-propanediol, and the specific reaction formula is as follows:

[0091]

[0092] 2-Hydroxymethyl-2-nitro-1,3-propanediol (2mol) was added to dichloroethane (4L), triethylamine (1.1L) was added, stirred, and toluoyl chloride (6.6mol) was added dropwise, After stirring, the system was heated to 50°C for 13 hours. Wash three times with water, three times with 0.5M hydrochloric acid, three times with saturated brine, dry and concentrate. The residue was recrystallized from ethanol to obtain 834 g of white powder with a yield of 90%.

[0093] 1 H NMR (CDCl 3 ,400MHz): δ7.95-7.28(m,15H),4.85(s 6H).

[0094] (2) prepare the compound shown in formula II by the compound shown in formula I, concrete reaction formula is as follows:

[0095]

[0096] The white powder (1.51mol) that obtains in step (1) is ad...

Embodiment 3

[0111] This embodiment prepares 3-oxetane carboxylic acid through the following steps

[0112] (1) The compound shown in formula I is prepared by 2-hydroxymethyl-2-nitro-1,3-propanediol, and the specific reaction formula is as follows:

[0113]

[0114] 2-Hydroxymethyl-2-nitro-1,3-propanediol (302g, 2mol) was added to dichloroethane (4L), triethylamine (1.1L) was added, stirred, and toluoyl chloride (8mol) was added dropwise , stirred, and the system was heated to 70°C for 8h. Wash three times with water, three times with 0.5M hydrochloric acid, three times with saturated brine, dry and concentrate. The residue was recrystallized from ethanol to obtain 852 g of white powder with a yield of 92%.

[0115] 1 H NMR (CDCl 3 ,400MHz): δ7.95-7.28(m,15H),4.85(s 6H).

[0116] (2) prepare the compound shown in formula II by the compound shown in formula I, concrete reaction formula is as follows:

[0117]

[0118] Add the white powder (700g, 1.51mol) obtained in step (1) int...

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 provides a preparation method of 3-oxetanecarboxylic acid. According to the preparation method, 2-hydroxymethyl-2-nitro-1,3-propylene glycol is taken as a raw material, hydroxyl in 2-hydroxymethyl-2-nitro-1,3-propylene glycol is subjected to a group protection reaction, nitryl in 2-hydroxymethyl-2-nitro-1,3-propylene glycol is subjected to a reductive elimination reaction and hydrolysis reaction, and 2-hydroxymethyl-1,3-propylene glycol is obtained; 2-hydroxymethyl-1,3-propylene glycol is continuously subjected to a cyclization reaction and an oxidation reaction, and 3-oxetanecarboxylic acid is obtained. The provided preparation method can be completed only through five-step reactions; compared with existing preparation methods through ten-step reactions, the preparation method has the advantages that the reaction steps are greatly reduced, the reaction routes are greatly shortened, the overall yield is increased, and the final yield can be up to 50% or above on the basisof the raw material, namely, 2-hydroxymethyl-2-nitro-1,3-propylene glycol; the related reactions are simple, and the method is easy to operate and favorable for industrial production.

Description

technical field [0001] The invention belongs to the field of pharmaceutical intermediates and synthesis, and relates to a preparation method of 3-oxetanecarboxylic acid. Background technique [0002] 3-Oxetane carboxylic acid is a commonly used pharmaceutical intermediate, and it is an important synthetic module in organic synthesis, which can synthesize steroids and so on. The present synthetic method mainly takes malonic acid diester as raw material, and obtains through ten steps of reaction, and concrete reaction formula is as follows: [0003] [0004] However, in this route, the reaction steps are cumbersome, requiring ten steps of reaction, the total yield is very low, less than 50%, and most of the key steps require column chromatography purification, which is not suitable for industrial scale-up. [0005] At present, only CN106565637A discloses a kind of synthetic method of 3 oxetane acetic acid, and this synthetic method comprises step 1, 3 oxetanone and (benzyl...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07D305/08C07D305/06C07C29/09C07C31/22C07C67/297C07C69/78C07C201/12C07C205/15
CPCC07C29/095C07C67/297C07C201/12C07D305/06C07D305/08C07C31/22C07C69/78C07C205/15
Inventor 柴腾林增明
Owner SHANGHAI BALMXY PHARMA CO LTD