N-BUTYL-2-CHLORO-ACETAMIDE

Chloroacetyl chloride (0.2 mol, 15.9mL)(CAS: 79-04-9) in an ice bath was slowly added dropwise to moderate molar amount of n- butylamine (0.2mol, 14.83g) in dichloromethane (50 mL) and 20percent (mass percentage) of Aqueous NaOH as solvent, after the addition was complete, warmed to room temperature stirring was continued for 2h. Collect the organic phase, And a 5percent (mass percentage) of HCl and 5percent (mass percentage) NaHCO 3 and washed (3 × 25 mL of) theorganic phase was dried and filtered, and the solvent removed under reduced pressure to give the intermediatechloroacetyl -n- butylamine (Yield92percent). The intermediate product (0.05mol, 9.00g) and 5, 6, 7, 8-tetrahydropyrido[1, 2-α] Imidazole (0.05mol, 6.11g) (CAS: 34167-66-3) mixed in acetonitrile (50 mL), and Was added the reaction was refluxed for 18H, after the reaction with acetonitrile and recrystallized from ethyl acetateoperation, the product was collected Was [4C-imCH 2 CONHBu] Cl (yield89percent), after anion exchange resinobtained by [4C-imCH 2 CONHBu] OH.N-Butyl-2-chloro-acetamide; [0241] An argon-flushed vial was charged with 10 mL of DCM and chloroacetyl chloride (5.5 mmol, 621 mg). The solution was cooled to 0 °C and n-butylamine (5.0 mmol, 366 mg) was slowly added. Then KGeneral procedure: To a solution of the corresponding β-keto ester 1 (1.0 mmol) and TsNExample B Synthesis of (N-n-Butylcarbamoyl)methyltriphenylphosphonium Chloride A solution of triphenyl phosphine (26.23 g, 0.1 mol) and n-butyl chloroacetamide (14.96 g, 0.1 mol) in toluene (250 mL) was refluxed with stirring for 22 h. After cooling to room temperature, the mixture was filtered and dried under high vacuum to afford 36.72 g (89.1% yield) of the title compound as white crystals. This material was used without further purification. Spectroscopic data were as follows: 1 H NMR (DMSO-d6, 270 MHz): delta=9.209 (1H, t, J=5.5 Hz, NH), 7.786 (15H, m, 3 C6 H5), 5.141 (2H, d, Jp =15.3 Hz, PCH2), 2.912 (2H, m, NCH2), 1.127 (4H, m, CH2 CH2), and 0.752 (3H, t, J=7.2 Hz, CH3).Chloroacetyl chloride (0.2 mol, 15.9mL)(CAS: 79-04-9) in an ice bath was slowly added dropwise to moderate molar amount of n- butylamine (0.2mol, 14.83g) in dichloromethane (50 mL) and 20% (mass percentage) of Aqueous NaOH as solvent, after the addition was complete, warmed to room temperature stirring was continued for 2h. Collect the organic phase, And a 5% (mass percentage) of HCl and 5% (mass percentage) NaHCO 3 and washed (3 × 25 mL of) theorganic phase was dried and filtered, and the solvent removed under reduced pressure to give the intermediatechloroacetyl -n- butylamine (Yield92%). The intermediate product (0.05mol, 9.00g) and 5, 6, 7, 8-tetrahydropyrido[1, 2-alpha] Imidazole (0.05mol, 6.11g) (CAS: 34167-66-3) mixed in acetonitrile (50 mL), and Was added the reaction was refluxed for 18H, after the reaction with acetonitrile and recrystallized from ethyl acetateoperation, the product was collected Was [4C-imCH 2 CONHBu] Cl (yield89%), after anion exchange resinobtained by [4C-imCH 2 CONHBu] OH.N-Butyl-2-chloro-acetamide; [0241] An argon-flushed vial was charged with 10 mL of DCM and chloroacetyl chloride (5.5 mmol, 621 mg). The solution was cooled to 0 C and n-butylamine (5.0 mmol, 366 mg) was slowly added. Then K2CO3 (5.5 mmol, 760 mg) was added and the mixture was agitated for 2h. The reaction mixture was filtered and concentrated in vacuo. Yield: 584 mg (86%). 1H NMR (400 MHz, CDCl3) delta 6.60 (s, IH), 4.00 (s, 2H), 3.32-3.22 (m, 2H), 1.56- 1.44 (m, 2H), 1.40-1.16 (m, 4H)5 0.91 (t, J=7.3, 3H), 0.89 (t, J=6.6, 3H). (100 MHz, CDCl3) delta: 165.8, 42.8, 39.7, 31.5, 20.1, 13.7.General procedure: To a magnetically stirred solution of substituted aniline 1 (50.0 mmol, 1.0 equiv) and K2CO3 (75.0 mmol, 1.5 equiv) in MeCN (100 mL), cooled in an ice bath, the chloroacetyl chloride (55.0 mmol, 1.1 equiv) was added dropwise. The reaction mixture was stirred at room temperature and monitored by TLC. After the completion of the reaction, the solvents were removed under vacuum and water (50 mL) was added into the residue. The mixture was then extracted with ethyl acetate (4 x 50 mL). The organic layers were combined, dried over anhydrous MgSO4, and evaporated under vacuum to give the crude product 2 without further purification.General procedure: To a magnetically stirred solution of substituted aniline 1 (50.0 mmol, 1.0 equiv) and K2CO3 (75.0 mmol, 1.5 equiv) in CH2Cl2 (100 mL), cooled in an ice bath, the chloroacetyl chloride (60.0 mmol, 1.2 equiv) was added dropwise. The reaction mixture was stirred at room temperature and monitored by TLC (Indine as streak reagent). After the completion of the reaction, the solvents were removed under vacuum and water (50 mL) was added into the residue. The mixture was then extracted with ethyl acetate (3 x 50 mL). The organic layers were combined, dried over anhydrous MgSO4, and evaporated under vacuum to give the crude product 2 without further purification.N-butylamine (585.1 mg, 8.0 mmol)Potassium carbonate (1.33 g, 9.6 mmol) was placed in 8 mL of dichloromethane solution, Ice bath, Chloroacetyl chloride (903.5 mg, 8.0 mmol) was slowly added dropwise to the above reaction flask, Room temperature overnight.After the reaction, Add the right amount of water, Extracted three times with methylene chloride, Combined with organic saturated saturated brine, Dried over anhydrous magnesium sulfate, Distillation under reduced pressure to give the crude product as a yellow oily liquid, Yield: 86.1%.In the 100 ml is provided with a thermometer, a stirring device, of the reflux condensation tube in three-opening bottle, adding 0.012 muM n-butylamine, 0.02 muM triethylamine, 20 ml dichloromethane, the constant pressure in the dropping funnel adding 0.01 muM chloro acetyl chloride (acyl chloride: n-butylamine molar ratio is preferably 1:1 - 1.4), is stirred under room temperature water bath, while stirring drips into the chlorine acetyl chloride (15 s/d), make it react sufficiently, after dropping, and then reacting 30min. Then into the water bath distillation device, remove excess triethylamine and dichloromethane, then obtaining the solid crude product. After cooling, water washing several times just the obtained solid crude product, and the funnel is conducted for (re-water washing several times), remove the layer an oily substance is placed in the beaker spare.A mixture of n-butylamine (585.1 mg, 8.00 mmol)Potassium carbonate (1.3 g, 9.60 mmol)Placed in 8mL methylene chloride solution, Ice bath, Chloroacetyl chloride (903.5 mg, 8.00 mmol) was slowly added dropwise to the above reaction flask, Room temperature overnight.After completion of the reaction, the appropriate amount of water, dichloromethane extraction, Combined with organic saturated brine, washed with anhydrous magnesium sulfate, Distillation under reduced pressure to give the crude product as a yellow oily liquid. Yield: 86.1%.General procedure: To a magnetically stirred solution of substituted aniline 1 (50.0 mmol, 1.0 equiv.) and K2CO3 (75.0 mmol, 1.5 equiv.) in CH2Cl2 (100 mL), cooled in an ice bath, the chloroacetyl chloride (60.0 mmol, 1.2 equiv.) was added dropwise slowly. The reaction mixture was stirred at room temperature and monitored by TLC (iodine as streak reagent). After the reaction was completed, the solvent was removed under vacuum and ice water (50 mL) was added into the residue. The mixture was then extracted with ethyl acetate (3 × 50 mL). The organic layers were combined, dried over anhydrous MgSO4, and evaporated under vacuum to give the crude product 2 without further purification.Weigh 72.20 mmol of n-butylamine and 114.20 mmol of potassium carbonate, add 150 mL of methylene chloride, cool to 0-5 C. in an ice bath, add 7.0 mL of chloroacetyl chloride, and react at room temperature for 3 h to obtain N-butyl-2-chloride. 6.67 g of crude acetamide; take N-n-butyl-2-chloroacetamide crude product and 4.27 g of o-chlorophenol in NaH/DMF overnight to obtain N-n-butyl-2-(2-chlorophenoxy) Acetamide.General procedure: Triethylamine (0.3643 g, 3.6 mmol) was added to a solution of the appropriate alkylamine or substituted benzylamine 5a-l (3 mmol) in dichloromethane (7.5 mL), and the reaction mixture was stirred for 5 min at room temperature, then 2-chloroacetyl chloride (0.3857 g, 3.6 mmol) was added dropwise to this reaction mixture at 0 C and stirred for 15 min at room temperature. After completion of the reaction, the solvent was evaporated under reduced pressure to afford 6a-l. KI (0.5976 g, 3.6 mmol) and CTAB (98.40 mg, 7.5% mmol) were added to a solution of the crude product 6a-l in acetone (30 mL) and maintained stirring at reflux for 2 h to afford 7al. K2CO3 (0.2073 g, 3 mmol) was added to a solution of scopoletin (0.3843 g, 2 mmol) in acetone (30 mL), and the reaction mixture was stirred at refluxed for 30 min. Then crude intermediates 7a-l were added into the mixture and maintained reflux for 8-12 h (the reaction progress was monitored by TLC with UV detection). After cooling the reaction and filtration, the solvent was evaporated under reduced pressure, and the residue was dissolved in ethyl acetate, washed with saturation sodium bicarbonate, and saturation salt solution successively, dried over anhydrous sodium sulfate, evaporated under reduced pressure to give the target crude products. The crude products were purified by column chromatography using petroleum ether/ethyl acetate from 6:1 to 2:1 as the gradient eluent system to yield the products 26-37.General procedure: Various substituted anilines were dissolved in glacial acetic acidat 0 C, to this was added over 30 min choloroacetylchloride (2equivalents). The reaction mixture was brought to room temperatureand stirred overnight. Saturated sodium bicarbonate solutionwas added till complete neutralization. The resulting precipitatewas filtered off and washed with n-hexane and dried. The resultantproduct was used further without any purification. Either of 3-hydroxy benzaldehyde, 4-hydroxy benzaldehyde, vanillin or isovanillin(1 equivalent) was dissolved in acetone and potassiumcarbonate (2 equivalents) was added. Then correspondingsubstituted acetamide was mixed to the stirring solution. Finally, potassium iodide (1.5 equivalent) was added. The reaction mixturewas refluxed for 8-10 h. After completion of reaction, the resultantmixture was concentrated and treated with water and extractedwith ethyl acetate (3 x 20 mL). The organic layers were combinedand treated with brine and dried over sodium sulfate andconcentrated. The crude mixture was purified over silica gel(60-120) using petroleum ether: ethyl acetate (9:1).General procedure: Various substituted anilines were dissolved in glacial acetic acid at0 C, to this was added over 30 min choloroacetyl chloride (2 equivalents).The reaction mixture was brought to room temperature andstirred overnight. Saturated sodium bicarbonate solution was added tillcomplete neutralization. The resulting precipitate was filtered off andwashed with n-hexane and dried. The resultant product (1) was usedfurther without any purification. Either of 4-hydroxy benzaldehyde(2a), vanillin (2b) or isovanillin (2c) (1 equivalent) was dissolved inacetone and potassium carbonate (2 equivalents) was added. Thencorresponding substituted acetamide (1) was mixed to the stirring solution.Finally, potassium iodide (1.5 equivalent) was added. The reactionmixture was refluxed for 8-10 h. After completion of reaction, the resultant mixture was concentrated and treated with water andextracted with ethyl acetate (3×20 mL). The organic layers werecombined and treated with brine and dried over sodium sulfate andconcentrated. The crude mixture was purified over silica gel (60-120)using petroleum ether: ethyl acetate (9:1).General procedure: The substituted primary amine 1 (60 mmol, 1.0 equiv.) and K2CO3 (75.0 mmol, 1.5 equiv.) were mixed in CH2Cl2 (80 mL) and cooled to 0 oC in an ice bath, to which the chloroacetyl chloride (72.0 mmol, 1.2 equiv.) was added dropwise. The reaction mixture was then stirred at room temperature and monitored by thin-layer chromatography (TLC, eluent: 25% ethyl acetate in petroleum ether). After the completion of the reaction, the solvent was removed under vacuum and water (50 mL) was added into the residue. The mixture was then extracted with ethyl acetate (50 mL x 3). The organic layers were combined, which was then washed with the saturated aqueous NaCl (100 mL), and dried over anhydrous Na2SO4. After the Na2SO4 was filtered and the filtrate was evaporated under vacuum to give the crude product 2 (N-substituted-2-chloroacetamide) without further purification. The mixture of crude N-substituted-2-chloroacetamide 2 (24 mmol, 1.2 equiv.), 2-chloro-4-substituted-phenol 3 (20 mmol, 1.0 equiv.), and sodium hydride (30 mmol, 1.5 equiv.) in DMF (60 mL) was refluxed and monitored by TLC (eluent: 25% ethyl acetate in petroleum ether). When the reaction was complete, the solvent was removed under vacuum and to the residue water (50 mL) was added. The mixture was then extracted by ethyl acetate (50 mL x 3), and the combined organic layers were evaporated at reduced pressure to give the crude product. The purification by column chromatography on silica gel (elute: ethyl acetate: petroleum ether = 1: 4) gave N-alkyl-2-(2-chloro-4-substituted-phenoxy)ethanamide 4 as the final product.

Molecular Weight:149.62
XLogP3:1.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:4
Exact Mass:149.0607417
Monoisotopic Mass:149.0607417
Topological Polar Surface Area:29.1
Heavy Atom Count:9
Complexity:85.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes