A kind of preparation method of 2-amino-5-fluorobenzonitrile
The technology of fluorobenzonitrile and amino group is applied in the field of preparation of 2-amino-5-fluorobenzonitrile, which can solve the problems of high cost, unfavorable industrialized amplification, long route and the like, and achieves the effects of short route and low raw material price.
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Embodiment 1
[0028] A preparation method of 2-amino-5-fluorobenzonitrile, said preparation method comprising the steps of:
[0029] (1) Add 142g (1mol) 2,5-difluorobenzaldehyde, 500ml dichloromethane, 83.4g (1.2mol) hydroxylamine hydrochloride, 202g (2mol) triethylamine to the reaction flask, and stir the reaction at 20°C after adding After 4 hours, the reaction was tracked by HPLC until the reaction of 2,5-difluorobenzaldehyde was complete; 1000ml of water was added to wash the organic layer, and the organic layer was concentrated to obtain 149.2g of compound III, with a molar yield of 95%.
[0030] (2) Add 78.5g (0.5mol) of compound III, 200ml of N,N-dimethylformamide, 153g (1mol) of phosphorus oxychloride to the reaction flask, stir at 80°C for 6 hours after the addition, and follow the reaction by HPLC until the compound III reacted completely; quenched into 1000ml of ice water, filtered and dried to obtain 59g of compound IV, molar yield: 85%.
[0031] (3) Add 41.7g (0.3mol) of compo...
Embodiment 2
[0035] A preparation method of 2-amino-5-fluorobenzonitrile, said preparation method comprising the steps of:
[0036] (1) Add 142g (1mol) 2,5-difluorobenzaldehyde, 500ml chloroform, 90.35g (1.3mol) hydroxylamine hydrochloride, 202g (2mol) triethylamine to the reaction flask, and stir at 30°C after adding After reacting for 2 hours, follow the reaction by HPLC until the reaction of 2,5-difluorobenzaldehyde is complete; add 1000ml of water to wash the organic layer, and concentrate the organic layer to obtain 146g of compound III, with a molar yield of 93%.
[0037] (2) Add 78.5g (0.5mol) of compound III, 200ml of N,N-dimethylformamide, 191.3g (1.25mol) of phosphorus oxychloride to the reaction flask, stir at 60°C for 2 hours after the addition, and follow the reaction by HPLC Until compound III reacted completely; quenched into 1000ml of ice water, filtered and dried to obtain 61.2g of compound IV, molar yield: 88%.
[0038] (3) Add 41.7g (0.3mol) of compound IV and 100ml of ...
Embodiment 3
[0040] A preparation method of 2-amino-5-fluorobenzonitrile, said preparation method comprising the steps of:
[0041] (1) Add 142g (1mol) 2,5-difluorobenzaldehyde, 500ml ethyl acetate, 97.3g (1.3mol) hydroxylamine hydrochloride, 202g (2mol) triethylamine to the reaction flask, and stir at 40 degrees for 3 hours after adding , HPLC followed the reaction until the reaction of 2,5-difluorobenzaldehyde was complete; 1000ml of water was added to wash the organic layer, and the organic layer was concentrated to obtain 144.4g of compound III, with a molar yield of 92%.
[0042] (2) Add 78.5g (0.5mol) of compound III, 200ml of N,N-dimethylformamide, 229.5g (1.5mol) of phosphorus oxychloride to the reaction flask, stir at 40°C for 4 hours after the addition, and follow the reaction by HPLC Until compound III reacted completely; quenched into 1000ml of ice water, filtered and dried to obtain 64g of compound IV, molar yield: 92%.
[0043] (3) Add 41.7g (0.3mol) of compound IV and 100ml...
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