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A kind of preparation method of tert-butyl 4-oxo-3,4-dihydropyridine-1(2h)-carboxylate

A technology of tert-butyl carboxylate and dihydropyridine is applied in the field of preparation of 4-oxo-3,4-dihydropyridine-1-tert-butyl carboxylate, and can solve the problems of long preparation route, low yield, Difficulty in product separation and purification, to achieve the effects of short reaction time, high yield and easy operation

Active Publication Date: 2022-03-18
南京合巨药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0016] Therefore, the technical problem to be solved in the present invention is to overcome the preparation route of 4-oxo-3,4-dihydropyridine-1 (2H)-tert-butyl carboxylate in the prior art, low yield, product separation Purification is difficult or the use of high-risk raw materials and reagents is defective, thereby providing a preparation method for tert-butyl 4-oxo-3,4-dihydropyridine-1(2H)-carboxylate, which can be quickly and efficiently through one-step reaction tert-butyl 4-oxo-3,4-dihydropyridine-1(2H)-carboxylate

Method used

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  • A kind of preparation method of tert-butyl 4-oxo-3,4-dihydropyridine-1(2h)-carboxylate
  • A kind of preparation method of tert-butyl 4-oxo-3,4-dihydropyridine-1(2h)-carboxylate
  • A kind of preparation method of tert-butyl 4-oxo-3,4-dihydropyridine-1(2h)-carboxylate

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] 3-Bromo-4-oxopiperidine-1-carboxylic acid tert-butyl ester (VI) (32.00g, 0.115mol, 1.0equiv.) was dissolved in 200mL DMF, LiBr (16.99g, 0.196mol, 1.7equiv.) was added .) and lithium carbonate (21.24g, 0.288mol, 2.5equiv.), stirred and reacted at 90°C for 0.5h, and the reaction was complete as detected by TLC. The reaction was cooled to room temperature, poured into 2L of water, extracted with ethyl acetate (200mL*2), and combined the organic phases. The organic phase was washed with saturated brine (300mL*3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a yellow oil, which became solid after standing for a period of time, beaten with n-heptane, filtered and dried to obtain a white solid 4-oxo - 15.09 g of tert-butyl 3,4-dihydropyridine-1(2H)-carboxylate. Yield: 66.5%. The reactions involved in this process are:

[0036]

[0037] Such as figure 1 as shown, 1 HNMR (400MHz, CDCl 3 ): δ (ppm) 7.82 (brs, 1H), 5.31 (d, J = 8....

Embodiment 2

[0040] 3-Bromo-4-oxopiperidine-1-carboxylic acid tert-butyl ester (VI) (20.00g, 0.072mol, 1.0equiv.) was dissolved in 100mL NMP, and LiBr (18.73g, 0.216mol, 3.0equiv. ), react at 110° C. for 0.5 h, and TLC detects that the reaction is complete. The reaction was cooled to room temperature, poured into 1L of water, extracted with ethyl acetate (100mL*2), and combined the organic phases. The organic phase was washed with saturated brine (200mL*3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a yellow oil, which was placed in a refrigerator to precipitate a solid, beaten with n-heptane, filtered and dried to obtain a white solid 4-oxo-3 , 6.80 g of tert-butyl 4-dihydropyridine-1(2H)-carboxylate. Yield: 48.0%.

Embodiment 3

[0042]Dissolve tert-butyl 3-bromo-4-oxopiperidine-1-carboxylate (VI) (10.00g, 0.036mol, 1.0equiv.) in 100mL N,N-dimethylacetamide, add sodium carbonate (15.24g, 0.144mol, 4.0equiv.), react at 80°C for 1h, and TLC detects that the reaction is complete. The reaction was cooled to room temperature, poured into 1L of water, extracted with ethyl acetate (100mL*2), and combined the organic phases. The organic phase was washed with saturated brine (200 mL*3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a yellow oil, which was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 6: 1) as a white solid 4-oxo 2.71 g of tert-butyl generation-3,4-dihydropyridine-1(2H)-carboxylate, yield 38.3%.

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Abstract

The invention discloses a preparation method of tert-butyl 4-oxo-3,4-dihydropyridine-1(2H)-carboxylate, which comprises: 3-bromo-4-oxopiperidine-1-carboxylate The acid tert-butyl ester is dissolved in a solvent, and a base is added to obtain 4-oxo-3,4-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester after reaction. The preparation method of 4-oxo-3,4-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester provided by the invention, the raw material 3-bromo-4-oxopiperidine-1-carboxylic acid tert-butyl Butyl ester, lithium bromide, lithium carbonate and other sources are widely available, cheap and easy to obtain, and only one step reaction can be used to obtain tert-butyl 4-oxo-3,4-dihydropyridine-1(2H)-carboxylate quickly and efficiently.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a preparation method of tert-butyl 4-oxo-3,4-dihydropyridine-1(2H)-carboxylate. Background technique [0002] 4-Oxo-3,4-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester (I) is an important intermediate, which can be used for 1,4-copolymerization with boron reagents, zinc reagents, aluminum reagents, etc. Conjugate addition reaction is an important raw material for the synthesis of chiral piperidones. I is widely used in the synthesis of piperidine-containing alkaloids and drug molecules, and has broad market prospects. [0003] 4-oxo-3,4-dihydropyridine-1 (2H)-carboxylate tert-butyl carboxylate (I) reported synthetic technique has following several: [0004] Chem.Commun.2005, 1711-1713 reported a method for preparing I from 4-methoxypyridine (II), II was reduced by tris(isopropoxy)potassium borohydride, reacted with BOC-anhydride, acidic conditions Under demethylation, o...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D211/86
CPCC07D211/86
Inventor 潘国骏李健
Owner 南京合巨药业有限公司