Novel synthesis method for 3-nitryl-4-benzyloxy-alpha-bromoacetophenone

A technology of benzyloxyacetophenone and bromoacetophenone, which is applied in the field of synthesis of 3-nitro-4-benzyloxy-α-bromoacetophenone, can solve the difficulties in production operation and the high toxicity of acetonitrile , Difficult to deal with and other problems, to achieve the effect of controlling the by-product dibromo, short reaction time, and easy operation

Inactive Publication Date: 2013-03-06
HANGZHOU NORMAL UNIVERSITY
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Problems solved by technology

[0003] The most important starting material for preparing formoterol is exactly the 3-nitro-4-benzyloxy group-alpha-bromoacetophenone shown in the formula (I), and U.S. Patent No. 6,040,344 has reported that from compound (II ) to the preparation method of (I), there are following problems in this method: (1) do reaction solvent with a large amount of acetonitrile, and the toxicity of acetonitrile is big; (2) this method is to start dripping bromine when the temperature of reaction system reaches 50 ℃ , and maintain this temperature to react, so that bromine is easy to volatilize during the dropping process and the reaction process, so that the amount of bromine is large and the production operation is difficult; (3) because the reaction temperature is high, the by-product dibromide (III) It is easy to produce, the yield is reduced, only 63%, and it is difficult to handle after production

Method used

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  • Novel synthesis method for 3-nitryl-4-benzyloxy-alpha-bromoacetophenone
  • Novel synthesis method for 3-nitryl-4-benzyloxy-alpha-bromoacetophenone
  • Novel synthesis method for 3-nitryl-4-benzyloxy-alpha-bromoacetophenone

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Effect test

Embodiment 1

[0020] In a 500ml three-neck flask equipped with a stirrer, dropping funnel and thermometer, add 200ml of methanol, add 54.2g of 3-nitro-4-benzyloxyacetophenone and 2.7g of phosphorus tribromide under stirring, and stir to make the solid Dissolve, keep the temperature at 5°C, start to drop the mixed solution of bromine and methanol (mixed by bromine: methanol = 1:3 (mass ratio)), react at this temperature for 1 hour, the reaction is complete, use 36g of bromine, After the reaction, the precipitate in the reaction was obtained by suction filtration, rinsed with 100 ml of petroleum ether, and baked at 60° C. for 2 hours to obtain 60.6 g with a yield of 86.6%.

Embodiment 2

[0022] In a 500ml three-neck flask equipped with a stirrer, dropping funnel and thermometer, add 200ml of methanol, add 54.2g of 3-nitro-4-benzyloxyacetophenone and 1.7g of phosphorus trichloride under stirring, and stir to make the solid Dissolve, keep the temperature at 5°C, start to drop a mixed solution of bromine and methanol (mixed by bromine: methanol=1:3 (mass ratio)), react at this temperature for 2 hours, the reaction is complete, use 45g of bromine, After the reaction, the precipitate in the reaction was obtained by suction filtration, rinsed with 100 ml of petroleum ether, and baked at 60° C. for 2 hours to obtain 53.5 g with a yield of 76.4%.

Embodiment 3

[0024] Add 200ml of methylene chloride in a 500ml three-neck flask equipped with a stirrer, dropping funnel and thermometer, add 54.2g of 3-nitro-4-benzyloxyacetophenone and 2.7g of phosphorus tribromide under stirring, and stir The solid was dissolved, and the temperature was maintained at 0° C., and a mixed solution of bromine and dichloromethane (mixed by bromine:dichloromethane=1:3 (mass ratio)) was started to be added dropwise, and the reaction was completed after 1 hour of reaction at this temperature. Use 33g to remove bromine. After the reaction, suction filter to obtain the precipitate in the reaction. After rinsing with 100ml of petroleum ether, bake at 60°C for 2 hours to obtain 59.8g with a yield of 85.4%.

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Abstract

The invention discloses a novel synthesis method for 3-nitryl-4-benzyloxy-alpha-bromoacetophenone having a structure represented by the formula (I), comprising the steps of: taking 3-nitryl-4-benzyloxyacetophenone having a structure represented by the formula (II) as raw material and taking phosphor or halide thereof as a catalyst; dissolving at first the 3-nitryl-4-benzyloxyacetophenone having the structure represented by the formula (II) and the catalyst in a reactive solvent; dropwise adding a mixed solution of bromine and the reactive solvent while maintaining the temperature in a range from negative 5 to 10 DEG C, after the addition, reacting for 1-5 hours while maintaining the temperature in a range from negative 5 to 10 DEG C, and filtering, washing and drying to obtain the 3-nitryl-4-benzyloxy-alpha-bromoacetophenone; the reactive solvent is selected from one of the group consisting of: ethyl acetate, methanol, ethanol, methylene dichloride, methenyl chloride, ethylidene dichloride and methylbenzene. The invention is mild in reaction conditions, friendly in reaction environment, short in reaction time, high in product yield and suitable for industrial production.

Description

(1) Technical field [0001] The invention relates to a synthesis method of 3-nitro-4-benzyloxy-α-bromoacetophenone. (2) Background technology [0002] Formoterol (FORMOTEROL) is a new type of β2 adrenergic receptor agonist developed by Japan Yamanouchi Company, which can be used to treat acute and chronic bronchitis, nocturnal asthma, exercise-induced asthma, chronic obstructive pulmonary disease and non-asthmatic respiratory diseases in children , especially suitable for acute attacks of nocturnal asthma, is a highly efficient, highly selective, long-acting and significant anti-inflammatory drug. [0003] The most important starting material for preparing formoterol is exactly the 3-nitro-4-benzyloxy group-alpha-bromoacetophenone shown in the formula (I), and U.S. Patent No. 6,040,344 has reported that from compound (II ) to the preparation method of (I), there are following problems in this method: (1) do reaction solvent with a large amount of acetonitrile, and the toxici...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C205/45C07C201/12B01J27/14
Inventor 潘建林沈华锋
Owner HANGZHOU NORMAL UNIVERSITY
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