2-nitrophthalic acid (100. 0 g), acetic anhydride (1 L) was added to a hydrogenation kettle, heated to 80 ° C,After the raw material disappeared, the mixture was cooled to room temperature, 10percent Pd / C (3 g) was added, replaced with nitrogen twice, hydrogen was introduced to IMPa,The reaction is maintained at room temperature until no hydrogen is absorbed, vented, blown with nitrogen,Heated to 110-115 ° C reaction to the raw material or intermediate state disappeared,Hot filter, cooled to 0-5 ° C, filtered, washed with glacial acetic acid to give pale yellow crystals, dried 80. 6g, yield 83percent, HPLC 99. 0percent.
Reference：
[1] Patent: CN105294534, 2016, A, . Location in patent: Paragraph 0036; 0037
2
[ 5434-20-8 ]
[ 108-24-7 ]
[ 6296-53-3 ]
Yield
Reaction Conditions
Operation in experiment
78.5%
for 4 h; Reflux
Example 2;- The Example 1 of the 3-amino-phthalic acid 28.0g (0.15mol) by adding 250 ml of the flask, then adding acetic anhydride 100 ml, was heated to reflux for 4h. The reaction followed by TLC to obtain 3-acetamido-phthalic anhydride. After completion of the reaction, the reaction flask placed in an ice water bath and stirred for 15min, then the solid separated; of diethyl ether was added with stirring, suction filtered and washed with diethyl ether to give a pale yellow flaky solid obtained after drying weighed 24. 9g, yield 78 . 5percent. mp: 180~182 ° C. IR (KBr): 3351,1841 ; 1766 ; 1700 ; 1603 cm -1. 1 HNMR (400MHz, CDCl 3): 2.34 (s, 3H), 7.69 (d, J=7.3Hz, 1H), 7.82-7.93 (m, 1H), 8.97 (d, J=8.5Hz, 1H), 9.12 (s, 1H) .MS (EI): 205 [M +].
61%
at 0 - 5℃; for 4 h; Heating / reflux
A mixture of 3-aminophthalic acid (108 g, 596 mmol) and acetic anhydride (550 mL) was charged into a 1-L 3-necked round bottom flask equipped with a mechanical stirrer, a thermometer, and a condenser. The reaction mixture was refluxed for 3 hours, cooled to ambient temperature, and kept at 0-5° C. for another 1 hour. The crystalline solid was collected by vacuum filtration and washed with ether. The solid product was dried in vacuum at ambient temperature to a constant weight to yield 75 g (61percent yield) of 3-acetamidopthalic anhydride as a white product. The product in CDCl3 was characterized by a 1H NMR spectrum showing the following chemical shifts (δ in ppm): 2.21 (s, 3H), 7.76 (d, 1H), 7.94 (t, 1H), 8.42 (d, 1H), 9.84 (s, 1H).
61%
for 3 h; Reflux
A 1 L 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer,and condenser and charged with 3-aminophthalic acid (108 g, 596 mmol) and acetic anhydride (550mL). The reaction mixture was heated to reflux for 3 hours and cooled to ambient temperature andfurther to 0-5 ° C. for another 1 hour. The crystalline solid was collected by vacuum filtrationand washed with ether. The solid product was dried in vacua at ambient temperature to a constant weight, giving 75 g (61percent yield) of 3-acetamidopthalic anhydride as a white product. ‘H-NMR (CDC13) ö: 2.21 (s, 3H), 7.76 (d, 1H), 7.94 (t, 1H), 8.42 (d, 1H), 9.84 (s, 1H).
61%
for 3 h; Reflux
A I L 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with 3-aminophthalic acid (108 g, 596 mmol) and acetic anhydride (550 mL). The reaction mixture was heated to reflux for 3 hours and cooled to about 25 °C and further to 0-5 °C for another 1 hour. The crystalline solid was collected by vacuum filtration and washed with ether. The solid product was dried in vacuo at ambient temperature to a constant weight, giving 75 g (61percent yield) of 3-acetamidopthalic anhydride as a white product. 1H-NMR (CDCls) δ: 2.21 (s, 3H), 7.76 (d, 1H), 7.94 (t, 1H), 8.42 (d, 1H), 9.84 (s, 1H).
61%
for 3 h; Reflux
[0112j A 1 L 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with 3 -aminophthalic acid (108 g, 596 mmol) and acetic anhydride (550 mL). The reaction mixture was heated to reflux for 3 hours and cooled to ambient temperature and further to 0-5°C for another 1 hour. The crystalline solid was collected by vacuum filtration and washed with ether. The solid product was dried in vacuo at ambient temperature to a constant weight, giving 75 g (61percent yield) of 3-acetamidopthalic anhydride as a white product. ‘H-NMR (CDC13) ö: 2.21 (s, 3H), 7.76 (d, 1H), 7.94 (t, 1H), 8.42 (d, 1H), 9.84 (s, 1H).
61%
for 3 h; Reflux
A I L 3 -necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with 3- aminophthalic acid (108 g, 596 mmol) and acetic anhydride (550 mL). The reaction mixture was heated to reflux for 3 hours and cooled to about 25 °C and further to 0-5 °C for another 1 hour. The crystalline solid was collected by vacuum filtration and washed with ether. The solid product was dried in vacuo at ambient temperature to a constant weight, giving 75 g (61 > yield) of 3-acetamidopthalic anhydride as a white product. 1H-NMR (CDCI3) δ: 2.21 (s, 3H), 7.76 (d, 1H), 7.94 (t, 1H), 8.42 (d, 1H), 9.84 (s, 1H).
61%
for 3 h; Reflux
6.2.2. Preparation of 3-Acetamidophthalic Anhydride A 1 L 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with 3-aminophthalic acid (108 g, 596 mmol) and acetic anhydride (550 mL). The reaction mixture was heated to reflux for 3 hours and cooled to ambient temperature and further to 0-5° C. for another 1 hour. The crystalline solid was collected by vacuum filtration and washed with ether. The solid product was dried in vacuo at ambient temperature to a constant weight, giving 75 g (61percent yield) of 3-acetamidopthalic anhydride as a white product. 1H-NMR (CDCl3) δ: 2.21 (s, 3H), 7.76 (d, 1H), 7.94 (t, 1H), 8.42 (d, 1H), 9.84 (s, 1H).
61%
for 3 h; Reflux
[0187] A I L 3 -necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with 3-aminophthalic acid (108 g, 596 mmol) and acetic anhydride (550 mL). The reaction mixture was heated to reflux for 3 hours and cooled to ambient temperature and further to 0-5°C for another 1 hour. The crystalline solid was collected by vacuum filtration and washed with ether. The solid product was dried in vacuo at ambient temperature to a constant weight, giving 75 g (61percent yield) of 3-acetamidopthalic anhydride as a white product. 1H-NMR (CDC13) δ: 2.21 (s, 3H), 7.76 (d, 1H), 7.94 (t, 1H), 8.42 (d, 1H), 9.84 (s, 1H).
61%
for 3 h; Reflux
10215] A 1 L 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with 3-aminophthalic acid (108 g, 596 mmol) and acetic anhydride (550 mL). The reaction mixture was heated to reflux for 3 hours and cooled to about 25° C. and thrther to 0-5°C. for another 1 hout The crystalline solid was collected by vacuum filtration and washed with ethet The solid product was dried in vacuo at ambient temperature to a constant weight, giving 75 g (61percent yield) of 3-acetamidopthalic anhydride as a white product. ‘H-NMR (CDC13) ö: 2.21 (s, 3H), 7.76 (d, 1H), 7.94 (t, 1H), 8.42 (d, 1H), 9.84 (s, 1H).
61%
for 3 h; Reflux
A mixture of 3-aminophthalic acid (108 g, 596 mmol) and acetic anhydride (550 mE) was charged into a 1 -L 3-necked round bottom flask equipped with a mechanical stirrer, a thermometer, and a condenser. The reaction mixture was refluxed for 3 hours, cooled to ambient temperature, and kept at 0-5° C. for another 1 hout The crystalline solid was collected by vacuum filtration and washed with ether. The solid product was dried in vacuum at ambient temperature to a constant weight toyield 75 g (61percent yield) of 3-acetamidopthalic anhydride as a white product. The product in CDC13 was characterized by a ‘H NMR spectrum showing the following chemical shifts (ö in ppm): 2.21 (s, 3H), 7.76 (d, 1H), 7.94 (t, 1H), 8.42 (d, 1H), 9.84 (s, 1H).
728 g
Reflux
The unbaked product obtained in Example 1 was transferred to a 5 L three-necked flask, acetic anhydride (4. 5 L) was added,Heated to reflux for 1-2 hours, filtered while hot, washed with glacial acetic acid and then cooled to 0-5 ° C,Stir until the product is fully precipitated, filtered, washed with acetic acid,827 g of yellow needle-like crystals, about 12percent solvent, 728 g after drying, 75percent in two steps, HPLC 99.8percent.
Reference：
[1] Patent: CN105330587, 2016, A, . Location in patent: Paragraph 0035; 0036
[2] Patent: US2007/155791, 2007, A1, . Location in patent: Page/Page column 14
[3] Patent: WO2014/74846, 2014, A1, . Location in patent: Page/Page column 20; 21
[4] Patent: WO2014/151180, 2014, A1, . Location in patent: Paragraph 0073
[5] Patent: WO2015/175773, 2015, A1, . Location in patent: Paragraph 0112
[6] Patent: WO2016/25686, 2016, A1, . Location in patent: Paragraph 0095
[7] Patent: US9272035, 2016, B2, . Location in patent: Page/Page column 23
[8] Patent: WO2015/175956, 2015, A1, . Location in patent: Paragraph 0187
[9] Patent: US2016/128981, 2016, A1, . Location in patent: Paragraph 0215
[10] Patent: US9387195, 2016, B2, . Location in patent: Page/Page column 27
[11] Journal of the American Chemical Society, 1909, vol. 31, p. 489
[12] Patent: WO2016/174685, 2016, A1, . Location in patent: Page/Page column 11
[13] Patent: CN105294534, 2016, A, . Location in patent: Paragraph 0028; 0029
The compound of formula VII 0. 55mol, and 37percent concentrated hydrochloric acid was added 500mL one-neck flask 1L, 25 ° C was stirred for 15h, the water distilled off under reduced pressure, slurried with 300mL tetrahydrofuran 10min, the solvent was distilled off under reduced pressure was repeated twice to give an off-white solid 120g, Karl Fischer determination of water 0.5percent. This solid was added to a 2L four-neck flask, was added acetic anhydride 1. 2L, 100 ° C 15h reaction, acetic anhydride was distilled off under reduced pressure, cooling the residue was added 200 mL of methyl tert-butyl ether, heating 10min, filtered, washed with methyl tert-butyl ether was washed with 20mL solid was filtered, the filter cake was dried in vacuo at 40 ° C 5H, 94g of off-white solid, a yield of 83.3percent.
45 g
at 110℃; for 2 h;
A stirred solution of 3-aminophthalic acid hydrochloride (65.0gm) in acetic anhydride (195 ml) was heated to 110°C and maintained for 2.0 hr. The reaction mass was cooled to 5°C. The product was filtered, washed with cyclohexane and dried at 40°C for 6.0 hr to obtain 45.0gm of 3-acetamidophthalic anhydride.
Reference：
[1] Patent: CN105622380, 2016, A, . Location in patent: Paragraph 0064; 0065; 0066; 0067
[2] Patent: WO2017/33116, 2017, A1, . Location in patent: Paragraph 00114
5
[ 603-11-2 ]
[ 6296-53-3 ]
Reference：
[1] Journal of the American Chemical Society, 1909, vol. 31, p. 489
[2] Patent: US2012/276087, 2012, A1,
[3] Patent: WO2014/74846, 2014, A1,
[4] Patent: WO2015/175956, 2015, A1,
[5] Patent: WO2014/151180, 2014, A1,
[6] Patent: WO2015/175773, 2015, A1,
[7] Patent: WO2016/25686, 2016, A1,
[8] Patent: US9272035, 2016, B2,
[9] Patent: CN105330587, 2016, A,
[10] Patent: WO2016/174685, 2016, A1,
[11] Patent: CN105294534, 2016, A,
[12] Patent: WO2017/33116, 2017, A1,
6
[ 641-70-3 ]
[ 6296-53-3 ]
Reference：
[1] Annales Pharmaceutiques Francaises, 1958, vol. 16, p. 421,425
7
[ 6296-53-3 ]
[ 59434-19-4 ]
Reference：
[1] Bulletin de la Societe Scientifique de Bretagne, 1951, vol. 26, p. Sonderheft 5, S. 7, 96[2] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1952, vol. 235, p. 962
[3] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1950, vol. 231, p. 912
8
[ 6296-53-3 ]
[ 102308-43-0 ]
Reference：
[1] Bulletin de la Societe Scientifique de Bretagne, 1951, vol. 26, p. Sonderheft 5, S. 7, 96[2] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1952, vol. 235, p. 962
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