| 83% |
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 1h;Product distribution / selectivity; |
Step 1 : 4-Bromo-2-(tert-butyl)aniline (P25a)To a solution of 2-ferf-butylaniline (14.9 g, 100 mmol) was added a solution of NBS (17.8 g, 100 mmol) in DMF at rt. The reaction mixture was stirred for 1 h at rt, diluted with water (30 mL) and extracted with Et20 (3 x 250 mL). The organic layer was washed with brine, dried over Na2S0 , concentrated and purified by CC to give compound P25a (19 g, 83%). |
| 83% |
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; |
Step 1 : 4-Bromo-2-(tert-butvuaniline (P38a) To a solution of 2-(tert-butyl)aniline (14.9 g, 100 mmol) was added a solution of NBS (17.8 g, 100 mmol) in DMF at rt. The mixture was stirred overnight at rt, diluted with water (30 mL) and extracted with Et20 (3x 250 mL). The organic layer was washed with brine, dried over Na2S04, concentrated and purified by CC to give compound P38a (19 g, 83%). |
| 79% |
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 4h; |
Step 1: 4-Bromo-2-tert-butylaniline (19a) To a solution of NBS (218 mg, 1 mmol) in DMF was added a solution of 2-tert-butylaniline (149 mg, 1 mmol) in DMF at rt. The reaction mixture was stirred for 4 h at rt. After the reaction was completed (monitored by LC-MS), water (30 mL) was added and the reaction mixture was extracted with EA (150 mL). The organic layer was washed with brine and dried over Na2SO4, concentrated in vacuo and purified by CC (hexane/EA = 3:1) to give the title compound 19a (180 mg, 79%). |
| 79% |
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 4h; |
Step 1: 4-Bromo-2-tert-butylaniline (Pla) To a solution of NBS (218 mg, 1 mmol) in DMF was added a solution of 2-tert-butylaniline(149 mg, 1 mmol) in DMF at rt. The reaction mixture was stirred for 4 h at ii, then water (30mL) was added and the mixture was extracted with EA (150 mL). The organic layer waswashed with brine and dried over Na2SO4, concentrated and purified by CC (hexane/EA = 3/1)to give compound Pla (180 mg, 79%). |
| 79% |
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 4h; |
Step 1 : 4-Bromo-2-ferf-butylaniline (P1a) To a solution of NBS (218 mg, 1 mmol) in DMF was added a solution of 2-tert-butylaniline (149 mg, 1 mmol) in DMF at rt. The reaction mixture was stirred for 4 h at rt, then water (30 mL) was added and the mixture was extracted with EA (150 mL). The organic layer was washed with brine and dried over Na2S04, concentrated and purified by CC (hexane/EA = 3/1) to give compound P1a ( 80 mg, 79%). |
| 79% |
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 2h; |
To a solution of 2-tert-butyl- (10 mL, 67 mmol) in DMF (130 mL) was added N-bromosuccinimide (6.9 g, 80 mmol). The reaction was stirred at rt for 2 h and then partitioned between water and EtOAc. The aqueous phase was washed with additional EtOAc and the organic phases were combined, washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent: 10-100% EtOAc/heptane) to provide 4-bromo-2-(tert-butyl)aniline (12 g, 53 mmol, 79% yield). 1H NMR (400 MHz, DMSO-d6) delta ppm 7.10 (d, J=2.5 Hz, 1H), 7.03 (dd, J=8.5, 2.3 Hz, 1H), 6.61 (d, J=8.5 Hz, 1H), 4.97 (s, 2H), 1.31 (s, 9H). m/z (ESI, +ve ion): 229.8 (M+H)+. |
| 71% |
|
Example 1; Synthesis of 4-[2-(3-tert-Butyl-4-diethylaminophenyl)-2-hydroxyiminoethoxy]benzoic acid:; a. Preparation of 4-Bromo-2-tert-butylaniline:; 51.8 g (347 mmol) of 2-tert-butylaniline (commercial product marketed especially by the company Aldrich) are dissolved in 600 ml of glacial acetic acid. 900 ml of aqueous 48% hydrobromic acid are then added, and the reaction medium is then cooled to 0 C. 300 ml of DMSO are then added dropwise, after which the reaction medium is warmed to room temperature. After stirring for 4 hours, 250 ml of ethyl acetate are added, followed by 400 ml of 5N sodium hydroxide, and then 1.75 l of 10N sodium hydroxide, to bring the pH to 8. 250 ml of ethyl acetate are added and the medium is separated by settling of the phases. The aqueous phase is then re-extracted with 500 ml of ethyl acetate. The combined organic phases are then rinsed with 1 l of water, and then concentrated under reduced pressure. The residue obtained is purified by chromatography (eluent: 95/5 heptane/ethyl acetate). An orange-colored oil is obtained (m=56.2 g, yield=71%). |
| 65% |
|
25 g (168 mmol) of 2-tert-butylaniline are placed in 300 ml of acetic acid. 450 ml of aqueous HBr at 48% are added and the mixture is then cooled to 0 C. 150 ml of DMSO are added dropwise, the mixture having been brought back to ambient temperature is stirred for 2 hours and it is then poured into ice-cold water and basified to pH 10 with 5N NaOH. It is extracted with diethyl ether and the organic phase is then dried and concentrated to dryness. The residue is column-purified (95/5 heptane/EtOAc). 25.2 g of 4-bromo-2-tert-butylphenylamine are obtained in the form of a yellow oil (yield=65%). |
|
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0 - 20℃; |
To a solution of 2-t-butylaniline (45 g, 0.3 mol, 1 eq) in DMF (250 mL) was added NBS (53.6 g, 0.3 mmol, 1 eq) portionwise at 0 oC. The mixture was stirred at rt overnight, TLC indicated completion. The reaction was poured into ice-water (500 mL), extracted with EA (200 mL x 3). The combined organic layers were washed with brine (200 mLx3), dried over sodium sulfate, concentrated affording 4-bromo-2-t-butylaniline (75 g, crude, containing DMF) which was used in next step directly. 1HNMR (300 MHz, CDCl3): G 7.32 (s, 1 H), 7.14- 7.11 (d, J = 10.5 Hz, 1 H), 6.53 (d, J = 8.4 Hz, 1 H), 3.74 (br, 2 H), 1.41 (s, 9 H).^ |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
Life Science
For Research Only
100K+ Compounds
Competitive Price
1-2 Day Shipping
