* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With sodium fluoride In hexane at 80℃; for 20 h; Industrial scale
In a 1 L three-necked flask, 100 g of ,o-chloronitrobenzene 450 g of n-hexane and 10 g of sodium fluoride were successively added and the temperature was raised to 80 ° C, 60 g of ethanolamine was added dropwise, and the reaction was carried out at this temperature for 20 hours. Sampling analysis, control the HPLC content of raw materials less than 3percent That is to stop the reaction. 90 ° C under reduced pressure distillation of petroleum ether, adding methanol and water for crystallization, filtration, washing, drying to get red Color crystal powder N- (2-nitrophenyl) ethanolamine 103g, HPLC purity 99.6percent
Reference：
[1] Heterocycles, 1999, vol. 51, # 11, p. 2561 - 2573
[2] Journal of the American Chemical Society, 1939, vol. 61, p. 1321,1323,1324
[3] Helvetica Chimica Acta, 1936, vol. 19, p. 1029,1030, 1033
[4] Chemische Berichte, 1947, vol. 80, p. 263,270
[5] Patent: US2434564, 1943, ,
[6] Patent: US2338380, 1940, ,
[7] Journal of the American Chemical Society, 1937, vol. 59, p. 1681[8] Journal of the American Chemical Society, 1939, vol. 61, p. 1321,1323
[9] Helvetica Chimica Acta, 1934, vol. 17, p. 1516,1519
[10] Journal of the Chemical Society, 1951, p. 2225,2226, 2229
[11] Journal of the Chemical Society, 1952, p. 4406,4408
[12] Journal of the American Chemical Society, 1937, vol. 59, p. 2660
[13] Patent: US5149700, 1992, A,
[14] Patent: CN106366006, 2017, A, . Location in patent: Paragraph 0026; 0027; 0028; 0029; 0030; 0031
2
[ 141-43-5 ]
[ 1493-27-2 ]
[ 4926-55-0 ]
Yield
Reaction Conditions
Operation in experiment
82.9%
With potassium carbonate In ethanolReflux
2-fluoronitrobenzene (0.92 g, 6.53 mmol) and ethanolamine (1.19 g, 19.59 mmol) were dissolved in 20 mL ethanol, potassium carbonate (1.08 g, 7.83 mmol) was added and stirred under reflux for 5-6 hours, after the reaction solution was cooled, filtered, the filtrate was concentrated under reduced pressure, to obtain an orange solid, and 20 mL saturated brine was added, extracted with ethyl acetate (3×40 mL), the organic phases were combined, washed with a saturated brine, dried on anhydrous sodium sulfate, rotary evaporated, purified by silica gel column chromatography to obtain 2-nitro-N-(2-hydroxyethyl)aniline (0.98 g, yield 82.9percent).
Reference：
[1] Tetrahedron Letters, 2010, vol. 51, # 17, p. 2362 - 2365
[2] Tetrahedron, 1998, vol. 54, # 18, p. 4647 - 4654
[3] Green Chemistry, 2013, vol. 15, # 3, p. 798 - 810
[4] Chemical Communications, 2013, vol. 49, # 85, p. 9935 - 9937
[5] Patent: US2017/114085, 2017, A1, . Location in patent: Paragraph 0053
[6] Tetrahedron, 1998, vol. 54, # 18, p. 4647 - 4654
[7] Bulletin de la Societe Chimique de France, 1956, p. 311,315
[8] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 21, p. 4790 - 4793
[9] Tetrahedron Letters, 2006, vol. 47, # 38, p. 6899 - 6902
[10] Journal of Physical Organic Chemistry, 2011, vol. 24, # 8, p. 714 - 719
3
[ 577-19-5 ]
[ 141-43-5 ]
[ 4926-55-0 ]
Reference：
[1] Journal of Medicinal Chemistry, 1993, vol. 36, # 5, p. 572 - 579
[2] Tetrahedron, 2001, vol. 57, # 21, p. 4507 - 4522
[3] Journal of Organic Chemistry, 1959, vol. 24, p. 1042
[4] European Journal of Organic Chemistry, 2009, # 35, p. 6151 - 6159
[5] Angewandte Chemie - International Edition, 2018, vol. 57, # 50, p. 16464 - 16468[6] Angew. Chem., 2018, vol. 130, p. 16702 - 16706,5
4
[ 88-74-4 ]
[ 4926-55-0 ]
Reference：
[1] Patent: US5508467, 1996, A,
5
[ 627-11-2 ]
[ 88-74-4 ]
[ 4926-55-0 ]
Reference：
[1] Patent: US5508467, 1996, A,
6
[ 98395-65-4 ]
[ 4926-55-0 ]
[ 98395-66-5 ]
Reference：
[1] Journal of Organic Chemistry, 1985, vol. 50, # 23, p. 4499 - 4504
7
[ 98395-64-3 ]
[ 4926-55-0 ]
Reference：
[1] Journal of Organic Chemistry, 1985, vol. 50, # 23, p. 4499 - 4504
[2] Journal of Organic Chemistry, 1985, vol. 50, # 23, p. 4499 - 4504
8
[ 98395-65-4 ]
[ 4926-55-0 ]
Reference：
[1] Journal of the American Chemical Society, 1980, vol. 102, # 14, p. 4848 - 4849
[2] Journal of the American Chemical Society, 1980, vol. 102, # 14, p. 4848 - 4849
[3] Journal of Organic Chemistry, 1985, vol. 50, # 23, p. 4499 - 4504
With 5%-palladium/activated carbon; ammonium formate; In methanol; at 0 - 25℃; for 1h;
To a anhydrous methanol solution (5 C.) of 2-nitro-N-(2-hydroxyethyl)aniline (0.87 g, 4.80 mmol), ammonium formate (1.51 g, 24.0 mmol) and 5% Pd/C (1.60 g) were added, stirred and reacted at 0-25 C. for 1 hour, filtered, the filter residue was washed with methanol, the filtrate was concentrated under reduced pressure, producing a red solid, and 30 mL saturated brine was added, extracted with ethyl acetate (3×30 mL), the organic phases were combined, dried on anhydrous sodium sulfate, filtered, concentrated under reduced pressure, to obtain a white solid (0.67 g, 92%).
87%
With hydrazine hydrate; In ethanol; at 40℃; for 2h;Inert atmosphere;
To a stirred solution of <strong>[4926-55-0]2-[(2-nitrophenyl)amino]ethanol</strong> (5, 12.0g, 0.066mol) in ethanol (80mL) hydrazine hydrate (8.26g, 0.165mol) was added at ambient temperature, followed by addition of 600mg Raney-Ni in 5mL ethanol. The obtained suspension was stirred at 40C for 2h. The catalyst was collected by filtration and the filtrate was evaporated in vacuo. The obtained crystalline product was used in the next step without further purification. Yield: 8.75g (87%), EI-LRMS m/z 153.2= (M+H)+.
55%
With Aminoiminomethanesulfinic acid; sodium hydroxide; In ethanol; water; at 50℃; for 1.5h;
General procedure: A mixture of 3 (10 mmol) and NaOH (4.0 g, 100 mmol) was prepared in EtOH (5 mL) and H2O (15 mL). TDO (5.4 g, 50 mmol) was added in batches within 15 minutes to the mixture followed by stirring at 50 C. After completion of the reaction as indicated by TLC, cooled to room temperature, the precipitated solid was filtered out and washed with water to obtain compound 4.
In pyridine; (2S)-N-methyl-1-phenylpropan-2-amine hydrate;
EXAMPLE 7 Preparation of 2-nitro-N-(2-mesyloxyethyl)-aniline To a solution of 2.5 g (0.013 moles) of 2-nitro-N-(2-hydroxyethyl)-aniline in 25 ml of anhydrous pyridine 2.3 g (1.6 ml, 0.02 moles) of methanesulfonyl chloride are added drop by drop at 0 C. The reaction mixture is stirred for an hour, then poured into 200 ml of ice water. The crystals are filtered, washed thoroughly with water and dried. 3.1 g (91%) of the title compound are obtained in the form of yellowish red crystals. M.p.: 86-87 C. (ethanol). Analysis for C9 H12 N2 O3 S (Mw.: 260.3). Calculated: C 41.53%, H 4.65%, N 10.76%, S 12.32%. Found: C 41.76%, H 4.41%, N 10.63%, S 12.54%.
Preparation of 2-hydroxyethylamino-nitrobenzene 244.6 g of the carbamate obtained according to Stage 1 are introduced into 900 g of water and 236 g of ethanol, the mixture is heated to 60 C. and 340.4 g of 50% strength potassium hydroxide solution are added in the course of 1.5 hours. The reaction mixture is subsequently stirred at 60 C. for 2.5 hours, brought to pH 8.0 with glacial acetic acid and allowed to cool. The product which has precipitated is filtered off with suction, washed with water, and dried at 50 C. in vacuo. Yield: 168.8 g of yellow-red granules Purity: 95% Yield in % of theory, based on carbamate: 88% Yield in % of theory, based on 2-nitroaniline: 80.1% 2-Nitroaniline content: 1.3% Melting point: 68-70 C.
With hydrogenchloride; potassium hydroxide; sulfuric acid; calcium carbonate; In anhydrous ethylene glycol dimethyl ether; water;
EXAMPLE 1 Preparation of 2-hydroxyethylamino-nitrobenzene 60.1 g of calcium carbonate are added to a solution of 138.1 g of 2-nitroaniline in 360 g of monoethylene glycol dimethylether and 60 g of water. 150.0 g of 2-chloroethyl chloroformate are then metered in at 80 C. and the reaction is brought to completion by subsequent stirring at 80 C. 100 g of water and 8.7 g of 35% strength hydrochloric acid are then added, up to a pH of 1, and the lower aqueous phase is separated off. The upper organic phase is diluted with 90 g of monoethylene glycol dimethylether, and 370.6 g of a 50% strength potassium hydroxide solution are added at 15 C. The reaction mixture is then heated to 85 C. and subsequently stirred at 85 C. for 4 hours. Thereafter, 250 g of water are added and the lower salt-containing aqueous phase is separated off. First 500 g of water and then 9 g of 10% strength sulphuric acid are added to the yellow-red organic phase, up to a pH of 8.5. After the monoethylene glycol dimethyl ether has been distilled off and the residue has been cooled to 10 C., the product is obtained in the form of yellow-red crystals. Yield: 173.4 g Purity: 99.8%
Step 2) Preparation of 2-(2-Aminoanilino)ethanol According to the procedure of B. Agai, et al., Tetrahedron, 32, 839, (1976), a mixture of 2-(2-nitroanilino)ethanol (43.1 g, 0.237 mol), SnCl2.2 H2 O (267.0 g, 1.18 mol), and EtOH (400 mL), was heated under reflux for 4 hours. The mixture was cooled, made basic (pH8) with 2.5N NaOH, and filtered through Celite. The filtrate was concentrated to remove the EtOH and the aqueous phase was extracted with EtOAc. The combined extracts were washed with H2 O and brine, dried, and concentrated. Recrystallization from EtOH gave 31.0 g (86%) of a brown solid m.p. 105-106 C. NMR (DMSO-d6, 300 MHz): delta3.10 (t, J=5.6 Hz, 2H), 3.61 (s, 2H), 4.42 (s, 2H), 4.70 (t, J=5.6 Hz, 2H), 6.40-6.60 (m, 4H).
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