4-Morpholinoaniline

PURPLE TO BROWN CRYSTALLINE POWDER

4-(4-nitrophenyl) morpholine (0.600 g, 2.882 mmol) and methanol (60 ml) were added to the hydrogenation reaction vessel. 10percent Palladium on carbon (0.060 g) was added under nitrogen protection. The reaction system was replaced with hydrogen for 3-4 times, and was stirred under hydrogen pressure to react for 18 hours under 40°C. HPLC detected that the reaction has completed, and then the reaction solution was cooled to room temperature, and filtered through Celite. The residue was washed with methanol. The combined filtrate was concentrated under vacumm by rotary evaporator to give the solid desired product (0.500 g, HPLC purity: 97.1percent, yield: 97percent). General procedure: Afterwards, the obtained compound, 2a was hydrogenated. Pd/C (2.78mmol) was added to a stirred solution of 1-methyl-4-(2-methyl-4-nitrophenyl-piperazine (5.53mmol)) in methyl alcohol (15ml) in N4-Fluoronitrobenzene (382 mg, 2.7 mmol) was dissolved in DMSO (7 ml), potassium carbonate (561 mg, 4.0 mmol) and morpholine (472 mg, 5.4 mmol) were added, and the mixture was stirred at 90° C. overnight. 4-(4-Nitrophenyl)morpholine (2.20 g, 10.6 mmol) was dissolved in 12 mL of methanol.Replace the nitrogen, Add 30mg of 10percent palladium on carbon, The system replaces hydrogen three times, The reaction was stirred at room temperature for 17 h.Palladium charcoal is filtered off, The filtrate was dried to give a pale yellow oil, 1.65 g.Yield: 87.4percent.Compound 7-b (1.5 g, 7.21 mmol) and ammonium chloride (1.0 g, 18.03 mmol) were dissolved in 50percent ethanol-water (20 mL), Zn-powder (1.2 g, 18.03 mmol) was then added. The mixture was refluxed for 30 minutes. After cooled to room temperature, the mixture was filtrated. The filter cake was washed with ethanol (10 mL), the combined filtrate were concentrated under reduced pressure. The residue was diluted with water (50 mL) and extracted with ethyl acetate (50 mL×3), the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to give light brown solid 7-a (1.1 g, yield: 86percent), which was used directly for the next step without purification. LC-MS (ESI): m/z=179 [M+H]To a mixture of 5a (2.13g, 10mmol) in dry ethyl acetate was added 10percent Pd/C (0.5g), following the reaction mixture was stirred under hydrogen gas at 80°C for 12h. The reaction mixture was concentrated in vacuo and the crude product was purified by column chromatography (dichloromethane/methanol 15:1 by volume) to give 4-morpholinyl aniline 6a (1.5g, yield 85percent). Synthesis of 4-Morpholin-4-yl-phenylamine General procedure: A mixture of compounds 5a–e (0.05 mol) in ethanol was heated to 65 °C, FeClGeneral procedure: A mixture of compounds 5 or 7a-c (0.05 mol) in ethanolwas heated to 65 °C, FeCl3·6H2O (2.8 g, 1 mmol) and activatedcarbon (0.18 g, 15 mmol) were added, and 80percent hydrazinehydrate (25 g, 0.5 mol) was added dropwise at such arate to keep the temperature below 70 °C, the reaction washeated at reflux for 5 h and then cooled to room temperatureand concentrated. Water (100 mL) was added, the reactionsolution was extracted three times with CH2Cl2 (60 mL). Theorganic extracts were combined, dried over sodium sulfate, filtered, and concentrated to obtain the compounds 8a-d.4 g of iron powder, 30 mL of water and 0.5 mL of glacial acetic acid were added to a 100 mL round bottom flask and heated to reflux for 10 min.Then, a solution of 3.12 g (0.015 mol) of 4-(4-nitrophenyl)morpholine dissolved in 20 mL of methanol was added, the reaction was stirred, and the reaction was traced to the end point by TLC.A small amount of anhydrous sodium sulfite was added, and after cooling, the pH was adjusted to 8-9 with a 10percent sodium carbonate solution, and filtered through Celite.The filter cake was washed with hot ethanol, and the filtrate was evaporated to a solvent.Washed with saturated sodium carbonate solution and saturated sodium chloride solution, the organic phase was dried over anhydrous sodium sulfate, and concentrated to give a yellow solid 1.96g, Melting point: 132-133 ° C, yield 73percent.Weigh 4g of iron powder in a 100ml round bottom flask.Add 30 ml of water and 0.5 ml of glacial acetic acid.Activated under reflux for 10 min, Then weighed 3.12 g (0.015 mol) of the previous synthesis4-(4-nitrophenyl)morpholine in 20 ml of methanol, Add to the reaction bottle, TLC tracks the reaction, the reaction is complete, Add a small amount of anhydrous sodium sulfite, cool and then adjust the pH to 8-9 with 10percent sodium carbonate solution, filter with diatomaceous earth, filter cake with hot ethanol, until the filtrate is colorless, the filtrate is steamed a part of solvent After that, it was extracted with ethyl acetate, washed successively with saturated sodium carbonate solution and saturated sodium chloride solution, and the organic phase was dried over anhydrous sodium sulfate.Concentrated to give 1.96 g of a yellow solid.The yield was 73percent.REFERENCE EXAMPLE 20 REFERENCE EXAMPLE 20 Reference Example 20 10 (7.13 g, 34.26 mmol) and ammonium chloride (3.66 g, 68.52 mmol) were added to the reaction flask and 30 ml of MeOHAnd water (30 ml) was added with iron powder (7.67 g, 137.04 mmol) under stirring. The reaction was carried out at 60 ° C for 2 hours. The filter was washed with n-butanol and extracted with n-butanol (150 ml x 3) Washed with water, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure to give 4.15 g of a dark brown solid (yield: 68percent).General procedure: The compound S1 (261 mg, 1.25 mmol), iron powder (210 mg, 4.76 mmol, 3 equiv.) and ammonium chloride (335 mg, 6.27 mmol, 5 equiv.) were dissolved in methanol : water (2 : 1, 15 mL). The reaction mixture was heated at 100 °C overnight, cooled to RT, filtered through celite and the solvent was reduced under vacuum. The condensed mixture was extracted with DCM, washed with brine, dried with sodium sulfate and all solvent was evaporated to furnish the condensed residue, which was purified by flash chromatography (elution system - EA/Hexane = 1 : 1 ) to obtain the title compound (245 mg, 1.43 mmol).

4-Morpholinoaniline is a morpholine derivative used in the preparation of central nervous system (CNS) active agents. 4-Morpholinoaniline is also one of the primary aromatic amines used in the colour developing process in photographs.

Molecular Weight:178.23
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:178.110613074
Monoisotopic Mass:178.110613074
Topological Polar Surface Area:38.5
Heavy Atom Count:13
Complexity:149
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes