N-Boc-Nortropinone is a drug intermediate and an important precursor for the synthesis of various drugs, so it has important research significance. The following are several synthetic routes of N-Boc-Nortropinone:
1. Oxidation of amino aldehydes using pyrimidine as a catalyst
Here, we will introduce in detail a step of synthesizing N-Boc-Nortropinone by oxidation of aminoaldehyde using pyrimidine as a catalyst.
1.1. Prepare the required reagents first, including N-Boc-4-phenyl-2-pyrrolidone, 1-Bromo-4-phenylbutane, concentrated nitric acid, pyrimidine, cuprous chloride, tetraethylammonium hydroxide and ionized water.
1.2. Add N-Boc-4-phenyl-2-pyrrolidone and 1-Bromo-4-phenylbutane into a dry round bottom flask, and drop a small amount of tetraethylammonium hydroxide as a catalyst. The reaction bottle was placed on a magnetic stirrer and stirred for 16 hours under natural environment until the reaction was complete.
1.3. After the reaction is finished, wash the reaction solution with deionized water that is titrated with acetone and sediment-like sediment until the pH value reaches about 6. The washed reaction solution was filtered, and the acetone in the filtrate was evaporated to obtain a white solid.
1.4. Add the collected white solid into a beaker, then add concentrated nitric acid and pyrimidine to catalyze the reaction. Place the beaker in the heating peak configuration and monitor the temperature with a sensitive thermometer to ensure that the heat can be accurately controlled. The reaction temperature was maintained at 60°C and the addition of the acid catalyst was completed within 2 hours.
1.5. Dissolve cuprous chloride in deionized water while maintaining the temperature at 60 °C. After waiting for the solution to completely dissolve, slowly add it to the beaker. Continue to react for 30 minutes until the reaction is complete.
1.6. After the reaction, the reaction solution was filtered, and the remaining precipitate was dried. The obtained solid is N-Boc-Nortropinone. The product can be further purified and isolated to achieve higher purity.
In conclusion, the synthesis of N-Boc-Nortropinone by oxidation of aminoaldehyde using pyrimidine as a catalyst is not very complicated, but it is necessary to strictly control the reaction time and temperature to ensure the smooth progress of the reaction and obtain the desired product. At the same time, necessary treatment and purification are required after the reaction to ensure that the final product meets the required high purity standards.
2. Reduction method of benzo[c]cyclohexanone
First, benzo[c]cyclohexanone is reacted with isopropanol to obtain a reduced form of benzo[c]cyclohexanone. Then, the reduced product is reacted with N-Boc-amino-oxyacetone to obtain N-Boc-Nortropinone. This synthetic method needs to use a large amount of reducing agent, and the reducing effect of cyclohexanone needs to be precisely controlled, and the total yield is low.
3. Iodoacetone method
First, N-Boc-3-chloroacetone is reacted with aniline to obtain N-Boc-3-aminoacetone. Then, N-Boc-3-aminoacetone and iodoacetone undergo ethanolamine-catalyzed addition reaction to obtain N-Boc-Nortropinone. This reaction requires the use of a catalyst, and the reaction conditions need to be carefully grasped; moreover, multi-step reaction operations are required, and it is difficult to obtain a high yield in the preparation process.
4. Isomerization method:
Isomerization of N-Boc-3-aminoacetone gives N-Boc-Nortropinone. This isomerization method is easy to cause side reactions under improper reaction conditions, and the overall reaction yield is low.
N-Boc-Nortropinone is an important organic compound. For this compound, the method of isomerization can be used to generate a number of different isomers. This article will introduce the steps and specific operation process of this isomerization method.
Experimental principle:
N-Boc-Nortropinone is a double bond compound with an unstable monoolefinic structure. After being thermodynamically excited, the compound undergoes ring closure and forms a new molecular configuration. This configuration has different chemical and physical properties. This property forms the theoretical basis for the production of a number of different isomers of N-Boc-Nortropinone.
Experimental procedure
(1) Put compound A into a two-neck bottle, add chloroform, and prepare to a concentration of 10 mg/mL.
(2) Pour the entire compound A-chloroform solution into a three-necked flask equipped with a burette. At fixation, add 2 mL of anhydrous sodium hydroxide (NaOH) solution and flush the equilibrium with gas.
(3) At room temperature, slowly add 2 mL of anhydrous hydrochloric acid (HCl) solution and flush with nitrogen to mix well.
(4) Maintain the reagent reaction system for 1-2 hours at room temperature. After the reaction, the product preparation was transferred to a funnel.
(5) Add an equal amount of water, and extract the upper layer with chloroform and ethanol. The extracted organic layer was dried in a rotary evaporator and purified with a Rieger tube to yield isomeric product B.
(6) The isomer mixture was precipitated and dried with a rotary evaporator to produce isomer product C.
(7) Conduct comparative property analysis of isomeric products B and C.
Summary: The isomerization method of N-Boc-Nortropinone can be used to prepare various isomers, thereby obtaining different chemical and physical properties. Through the above experimental steps, we can obtain a relatively simple and practical method for preparing isomers, and also provide more methods for the research of organic chemistry.
In summary, the relatively mature synthetic route studied at present is to use benzo[c]cyclohexanone reduction method, using benzo[c]cyclohexanone as the original reactant, and obtaining benzo[c]cyclohexanone after reduction with isopropanol c] The reduced product of cyclohexanone, which finally reacts with N-Boc-amino-oxyacetone to obtain N-Boc-Nortropinone. Although there are certain defects, the overall reaction accuracy is high, and the total yield can roughly meet the synthesis requirements.