2-BROMO-4-TERT-BUTYLANILINE

To a solution of 4-tert-butylaniline (10 g, 68 mmol) in DMF (150 mL) cooled to 0 °C was added NBS (12.1 g, 68 mmol) under strictly exclusion of light, and the mixture was stirred for 30 min at the same temperature. Then the ice-bath was removed and the stirring was continued at rt overnight (18 h). The mixture was poured into water (300 mL) and extracted with CH2Cl2, the combined organic phase was over MgSO4 and filtered. he filtrate was evaporated to give a black-brown tar which was purified by column chromatography (PE : EtOAc = 20 : 1) to obtain a colorless oil (13.5 g, 87 percent); Rf = 0.69 (PE : EtOAc = 5 : 1); 1H-NMR (CDCl3, 300 MHz) δ: 7.43 (t, J = 1.2 Hz, 1H), 7.14 (m, 1H), 6.72 (d, J = 8.1 Hz, 1H), 3.96 (br, 2H), 1.30 (s, 9H).Prepared according to a literature procedure. To a solution of 4-(tertbutyl)aniline (5.50 mL, 34.5 mmol, 1.0 eq.) in chloroform (200 mL) at 0 °C wasadded N-bromosuccinimide (6.76 g, 37.9 mmol, 1.1 eq.). The reaction was warmed to room temperature and stirred for 5 hours, then washed with water and extracted into chloroform. The organic phase was dried over sodium sulphate and the solvent removed under reduced pressure. Purification by flash chromatography on silica gel (SiO2, hexane)afforded the title compound as a brown oil (5.35 g, 23.5 mmol, 68 percent yield).General procedure: To a solution of 2-bromoaniline (5 g, 29 mmol) dissolved in CH3CN (80 mL) was added aq. HCl (15 mL conc. HCl in 50 mL water), then the mixture was cooled to 0 C, and it was added a solution of NaNO2 (2.4 g, 34.87 mmol) in water (50 mL). After addition, the reaction was kept at the temperature lower than 5 C for 30 min and it was added a solution of (7.23 g, 43.59 mmol) in water (50 mL). After addition, the reaction was kept at room temperature overnight, poured into water (300 mL) and extracted with CH2Cl2.The organic phase was dried over MgSO4. After workup, the brown oily product was distilled to afford a pale-yellow.35.0 g (201.03 mmol) of NBS was slowly added dropwise to a solution of 30.0 g (201.03 mmol) of 4-tert-butyl aniline in 670 mL of acetonitrile, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, water was added thereto, followed by extraction with dichloromethane (DCM). The extracted organic layer was washed once with saturated brine and then distilled under reduced pressure. The residue was purified by column chromatography (CHCl3) to obtain 45.0 g (yield: 98.0%) of a yellow liquid compound (Intermediate (21)).To a solution obtained by dissolving 30.0 g (201.03 mmol) of 4-tert-butylaniline in 670 ml of acetonitrile, 35.8 g (201.03 mmol) of NBS was slowly added dropwisely at about 0 C., followed by stirring at room temperature for about 24 hours. After finishing the reaction, water was added and extraction was performed using dichloromethane (DCM). The organic layer thus extracted was washed with a saturated saline solution once and then, distilled under a reduced pressure. The crude product was separated by column chromatography (CHCl3) to obtain 45.0 g (yield: 98.0%) of a yellow liquid compound (Intermediate 41).To a solution of 4-tert-butylaniline (10 g, 68 mmol) in DMF (150 mL) cooled to 0 C was added NBS (12.1 g, 68 mmol) under strictly exclusion of light, and the mixture was stirred for 30 min at the same temperature. Then the ice-bath was removed and the stirring was continued at rt overnight (18 h). The mixture was poured into water (300 mL) and extracted with CH2Cl2, the combined organic phase was over MgSO4 and filtered. he filtrate was evaporated to give a black-brown tar which was purified by column chromatography (PE : EtOAc = 20 : 1) to obtain a colorless oil (13.5 g, 87 %); Rf = 0.69 (PE : EtOAc = 5 : 1); 1H-NMR (CDCl3, 300 MHz) delta: 7.43 (t, J = 1.2 Hz, 1H), 7.14 (m, 1H), 6.72 (d, J = 8.1 Hz, 1H), 3.96 (br, 2H), 1.30 (s, 9H).To a solution of 4-tert-butylaniline (1.0 g, 6.7 mmol) in N, N-dimethylformamide (15 mL) at 0 C was added N-bromosuccinimide (1.2 g, 6.7 mmol) under the exclusion of light and the mixture was stirred for 16 hours at room temperature. The reaction mixture was poured into water (30 mL) and extracted with dichloromethane (3 x 20 mL), dried over anhydrous magnesium sulfate and concentrated. The crude product was purified by flash column chromatography using ethyl acetate, hexane (1:19) as an eluent to obtain the title compound (1.2 g, 78%) as a brown oil, Rf: 0.46 (3:17 ethyl acetate, hexane); IR (vmax (film)): 3437, 3347, 2962, 1617, 1502, 1255, 824 cm-1; 1H NMR (300 MHz, CDCl3): delta 1.27 (9H, s), 3.92 (2H, bs), 6.72 (1H, d, J = 8.3 Hz), 7.14 (1H, d, J = 8.5 Hz), 7.41 (1H, s) ppm; 13C NMR (75 MHz, CDCl3): delta 31.5, 34.1, 109.4, 115.7, 125.5, 129.5, 141.6, 143.0 ppm; LRMS (+ESI) m/z: 228.0/230.0 ([M+H]+ 100%).Prepared according to a literature procedure. To a solution of 4-(tertbutyl)aniline (5.50 mL, 34.5 mmol, 1.0 eq.) in chloroform (200 mL) at 0 C wasadded N-bromosuccinimide (6.76 g, 37.9 mmol, 1.1 eq.). The reaction was warmed to room temperature and stirred for 5 hours, then washed with water and extracted into chloroform. The organic phase was dried over sodium sulphate and the solvent removed under reduced pressure. Purification by flash chromatography on silica gel (SiO2, hexane)afforded the title compound as a brown oil (5.35 g, 23.5 mmol, 68 % yield).To a solution of 4-tert-butyl-phenylamine (447 g, 3 mol) in DMF (500 mL) was added dropwise NBS (531 g, 3 mol) in DMF (500 mL) at room temperature. Upon completion, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with water, brine, dried over Na2SO4 and concentrated. The crude product was directly used in the next step without further purification.To a solution of 4-tert-butyl-phenylamine (447 g, 3 mol) in DMF (500 rnL) was added dropwise NBS (531 g, 3 mol) in DMF (500 mL) at room temperature. Upon completion, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with water, brine, dried over Na2SO4 and concentrated. The crude product was directly used in the next step without further purification.To a solution of 4-rert-Butyl-phenylamine (447 g, 3.00 mol) in DMF (500 mL) was added dropwise NBS (531 g, 3.00 mol) in DMF (500 mL) at room temperature. Upon completion, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with water, brine, dried over Na2SO4 and concentrated. The crude product was directly used in the next step without further purification.2-Bromo-4-tert-butyl-phenylamine To a solution of 4-tert-Butyl-phenylamine (447 g, 3.00 mol) in DMF (500 mL) was added dropwise NBS (531 g, 3.00 mol) in DMF (500 mL) at room temperature. Upon completion, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with water, brine, dried over Na2SO4 and concentrated. The crude product was directly used in the next step without further purification.Example 3 2-Bromo-4-tert-butyl-phenylamine To a solution of 4-tert-butyl-phenylamine (447 g, 3 mol) in DMF (500 mL) was added dropwise NBS (531 g, 3 mol) in DMF (500 mL) at room temperature. Upon completion, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with water, brine, dried over Na2SO4 and concentrated. The crude product was directly used in the next step without further purification.To a solution of 4-tert-butyl-phenylamine (447 g, 3 mol) in DMF (500 mL) was added dropwise NBS (531 g, 3 mol) in DMF (500 mL) at room temperature. Upon completion, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with water, brine, dried over Na2SO4 and concentrated. The crude product was directly used in the next step without further purification.To a solution of 4-tert-butyl-phenylamine (447 g, 3 mol) in DMF (500 mL) was added dropwise NBS (531 g, 3 mol) in DMF (500 mL) at room temperature. Upon completion, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with water, brine, dried over Na2SO4 and concentrated. The crude product was directly used in the next step without further purification.Diluted 7.46 g of 4-t-butylaniline with 100 ml of ethyl acetate under ice cooling9.08 g of N-bromosuccinimide was added and stirred, and then stirred overnight at room temperature. Water and methyl-t-butyl ether are added to the reaction solution, and the reaction solution is separated, and the organic layer is washed with water and brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue obtained is subjected to silica gel column chromatography (hexane : Ethyl acetate = 1: 0 to 10: 1), 8.5 g of 2-bromo-4-t-butylaniline was obtained.General procedure: To a stirred solution of 4-isopropylaniline (5 g, 37.0 mmol) in 100 mL DMF, 1- bromopyrrolidine-2, 5-dione (6.58 g, 37.0 mmol) was added at 0C. The reaction mixture was allowed to warm to room temperature and stirred overnight under the exclusion of light. The reaction was quenched by the addition of water and the organic contents were extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulphate and concentrated and the crude obtained was purified by column purification to give the product as a brown oil. (Yield = 5.45 g, 69%). NMR (400 MHz, Chloroform-if) delta 7.32 - 7.29 (m, 1H), 7.03 - 6.98 (m, 1H), 6.79 (d, J = 8.2 Hz, 1H), 2.81 (p, J = 6.9 Hz, 1H), 1.22 (d, J = 6.9 Hz, 6H).General procedure: To a solution of aniline (1.0 eq.) and pyridine (1.2 eq.) in DCM (0.2 M) at 0 C, was added the sulfonyl chloride (1.0 eq.). The reaction was gradually warmed to room temperature andstirred for 16 hours before quenching with water and stirring for a further 30 minutes. The reaction was then extracted into DCM and the organic phase was washed with HCl(aq) (1 M), saturated aqueous sodium bicarbonate and brine, dried over magnesium sulphate and the solvent removed under reduced pressure. Purification was performed by flash chromatography on silica gel

Molecular Weight:228.13
XLogP3:3.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:227.03096
Monoisotopic Mass:227.03096
Topological Polar Surface Area:26
Heavy Atom Count:12
Complexity:150
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes