Simple preparation process of 9-fluorenemethanol

Abstract

The invention relates to a method for preparation of 9-fluorenemethanol, especially to an improved preparation method of 9-fluorenemethanol. The method comprises the steps of: 1) preparing industrial fluorene, sodium ethoxide, ethyl formate and tetrahydrofuran in a ratio of 50g:15g:50ml:200ml, adding tetrahydrofuran of sodium ethoxide into a four-mouth bottle, controlling the temperature at 0-10DEG C, adding a tetrahydrofuran solution of industrial fluorene dropwisely, adding ethyl formate, and raising the temperature to 30-40DEG C, thus obtaining 9- fluorenecarboxaldehyde; and 2) adding methanol and NaBH4 under ice bath, conducting reduction to obtain a 9-fluorenemethanol crude product, carrying out recrystallization so as to obtain white needlelike 9-fluorenemethanol. The crude product purity is enhanced, the reaction conditions are mild, and the cost is lowered, so that the method is easy for industrialization.

Description

technical field

[0001] The invention relates to a method for preparing 9-fluorenemethanol, in particular to an improved method for preparing 9-fluorenemethanol from fluorene. Background technique

[0002] As an amino-protecting reagent, fluorenylmethoxycarbonyl chloride is widely used in the field of peptide synthesis. Its stability under acidic conditions and easy detachment under alkaline conditions play a great role in promoting the development of the biological field and the research and development of new drugs. Auxiliary role, 9-fluorenemethanol is used as a raw material for the preparation of fluorenylmethoxycarbonyl chloride intermediates. It is also an important drug itself, and has a good therapeutic effect on drug-resistant falciparum malaria and rodent malaria. It is used as a phosphoric acid in the synthesis of deoxyribonucleotides. The demand for ester protecting groups and carboxyl protecting groups is increasing; my country's industrial fluorene is rich in reso...

Examples

Embodiment 1

[0022] Preparation of 9-Fluorenaldehyde

[0023] Take 15g of sodium ethoxide and 100ml of tetrahydrofuran into a four-necked bottle, turn on the magnetic stirring, and after 30 minutes, dissolve 50g of industrial fluorene into 300-350ml of tetrahydrofuran and add it dropwise to the reaction bottle. After half an hour of dripping, react for 2-3 hours and add 100ml ethyl formate, molar equivalent 4-5, heat up to 30-40°C, react for about 12 hours, pour into ice water, wash with 100ml of petroleum ether in two equal parts, use acetic acid to make the water phase acidic, and use 200ml di Chloromethane was washed and extracted twice, and the organic phase was washed twice with saturated saline, left to stand and separated, dried with anhydrous sodium sulfate, filtered, concentrated and recovered to dichloromethane to obtain 9-fluorenaldehyde, no impurities on the TLC plate .

Embodiment 2

[0025] Preparation of 9-Fluorenaldehyde

[0026] Take 15g of sodium ethoxide and 50ml of dimethylformamide into a four-neck bottle, turn on the magnetic stirring, and after 30 minutes, dissolve 50g of industrial fluorene into 200-250ml of dimethylformamide and drop them into the reaction bottle, and drop them in half an hour After reacting for 2-3 hours, add 100ml of ethyl formate, raise the temperature to about 60°C, react for about 12 hours, pour into ice water, wash with 100ml of petroleum ether in two equal parts, use acetic acid to make the water phase acidic, and use 200ml of bismuth Chloromethane was washed and extracted twice, and the organic phase was washed twice with saturated saline, left to stand and separated, dried with anhydrous sodium sulfate, filtered, concentrated and recovered to dichloromethane to obtain 9-fluorenaldehyde, no impurities on the TLC plate .

Embodiment 3

[0028] Preparation of 9-fluorenemethanol

[0029] Under ice bath, mix the 9-fluorenaldehyde obtained in the previous step, 100-120ml methanol, about 5g NaBH 4 , added to a three-neck flask, stirred at room temperature for about 3 hours, then poured the reaction solution into water and stirred, and a large amount of white solid was formed. After filtration, the filter cake was vacuum-dried at 60°C for 2 hours to obtain about 49 g of The crude product of 9-fluorenylmethanol, the purity of 9-fluorenylmethanol in the crude product is about 92%, and the yield is about 84%.

[0030] Dissolve the crude product of 9-fluorenemethanol with a purity of about 92% according to the mass ratio of crude product:petroleum ether=1:12, then perform hot filtration, and slowly cool the filtrate to about 0°C, a large number of white needle-like crystals precipitate out , filtered, and vacuum-dried the filter cake at 60°C for 2 hours to obtain 9-fluorenemethanol with a purity greater than 99%; the ...

technical field

[0001] The invention relates to a method for preparing 9-fluorenemethanol, in particular to an improved method for preparing 9-fluorenemethanol from fluorene. Background technique

[0002] As an amino-protecting reagent, fluorenylmethoxycarbonyl chloride is widely used in the field of peptide synthesis. Its stability under acidic conditions and easy detachment under alkaline conditions play a great role in promoting the development of the biological field and the research and development of new drugs. Auxiliary role, 9-fluorenemethanol is used as a raw material for the preparation of fluorenylmethoxycarbonyl chloride intermediates. It is also an important drug itself, and has a good therapeutic effect on drug-resistant falciparum malaria and rodent malaria. It is used as a phosphoric acid in the synthesis of deoxyribonucleotides. The demand for ester protecting groups and carboxyl protecting groups is increasing; my country's industrial fluorene is rich in reso...

Examples

Embodiment 1

[0022] Preparation of 9-Fluorenaldehyde

[0023] Take 15g of sodium ethoxide and 100ml of tetrahydrofuran into a four-necked bottle, turn on the magnetic stirring, and after 30 minutes, dissolve 50g of industrial fluorene into 300-350ml of tetrahydrofuran and add it dropwise to the reaction bottle. After half an hour of dripping, react for 2-3 hours and add 100ml ethyl formate, molar equivalent 4-5, heat up to 30-40°C, react for about 12 hours, pour into ice water, wash with 100ml of petroleum ether in two equal parts, use acetic acid to make the water phase acidic, and use 200ml di Chloromethane was washed and extracted twice, and the organic phase was washed twice with saturated saline, left to stand and separated, dried with anhydrous sodium sulfate, filtered, concentrated and recovered to dichloromethane to obtain 9-fluorenaldehyde, no impurities on the TLC plate .

Embodiment 2

[0025] Preparation of 9-Fluorenaldehyde

[0026] Take 15g of sodium ethoxide and 50ml of dimethylformamide into a four-neck bottle, turn on the magnetic stirring, and after 30 minutes, dissolve 50g of industrial fluorene into 200-250ml of dimethylformamide and drop them into the reaction bottle, and drop them in half an hour After reacting for 2-3 hours, add 100ml of ethyl formate, raise the temperature to about 60°C, react for about 12 hours, pour into ice water, wash with 100ml of petroleum ether in two equal parts, use acetic acid to make the water phase acidic, and use 200ml of bismuth Chloromethane was washed and extracted twice, and the organic phase was washed twice with saturated saline, left to stand and separated, dried with anhydrous sodium sulfate, filtered, concentrated and recovered to dichloromethane to obtain 9-fluorenaldehyde, no impurities on the TLC plate .

Embodiment 3

[0028] Preparation of 9-fluorenemethanol

[0029] Under ice bath, mix the 9-fluorenaldehyde obtained in the previous step, 100-120ml methanol, about 5g NaBH 4 , added to a three-neck flask, stirred at room temperature for about 3 hours, then poured the reaction solution into water and stirred, and a large amount of white solid was formed. After filtration, the filter cake was vacuum-dried at 60°C for 2 hours to obtain about 49 g of The crude product of 9-fluorenylmethanol, the purity of 9-fluorenylmethanol in the crude product is about 92%, and the yield is about 84%.

[0030] Dissolve the crude product of 9-fluorenemethanol with a purity of about 92% according to the mass ratio of crude product:petroleum ether=1:12, then perform hot filtration, and slowly cool the filtrate to about 0°C, a large number of white needle-like crystals precipitate out , filtered, and vacuum-dried the filter cake at 60°C for 2 hours to obtain 9-fluorenemethanol with a purity greater than 99%; the ...