ChemicalBook CAS DataBase List 4-Bromo-3,5-dimethylaniline

4-Bromo-3,5-dimethylaniline synthesis

8synthesis methods

Product Name:4-Bromo-3,5-dimethylaniline
CAS Number:59557-90-3
Molecular formula:C8H10BrN
Molecular Weight:200.08

To a solution of 3,5-dimethylaniline (80 g, 660 mmol) in 800 mL MeCN was added a solution of NBS (117g, 660mmol) in 400 ml MeCN at an ice bath, stirred at room temperature for 16h. The reaction mixture was concentrated under reduced pressure. The residue was purified by silica column chromatography (Eluent C) to give title product 4-bromo-3,5-dimethylaniline 1b (90 g, yellow solid), yield 68.2 %.

108-69-0 Synthesis

108-69-0
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$9.00/1g

59557-90-3
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$20.00/1g

Yield:59557-90-3 96%

Reaction Conditions:

Stage #1: 3,5-dimethylaminoanilinewith trifluoroacetic anhydride in dichloromethane at 0; for 0.5 h;
Stage #2: with bromine in dichloromethane at 0; for 0.0833333 h;

Steps:

205

To a solution of 3,5-dimethylaniline (3.0 ml, 24 mmol) in ice cold dichloromethane (200 ml) was added trifluoroacetic anhydride (4.18mL, 1.25 equivs). After 30 minutes, bromine (1.2 ml, 0.97 equivs) was slowly added over 5 minutes. After aqueous work-up and drying in vacuo the recovered crude (6.81 g, 96%) was taken up in dry THF (40 ml). The solution was cooled to -78⁰C and methyl lithium'lithium bromide complex (21 ml, 1.3 equivs) was added. After 5 minutes, s-butyllithium (20 ml, 1.3 equivs) was added followed by di-t-butyldicarbonate (8.02 g, 1.6 equivs). Following aqueous work up the crude amide was taken up in a 3:1 solution of methanol: water (100 ml) followed by sodium hydroxide (5 ml, 1OM, 2 equivs). The reaction was stirred at 6O⁰C overnight. Solvent was removed and the crude was diluted with dichloromethane, washed with water, brine, and dried over sodium sulfate. The aniline was then taken up in dichloromethane (2 ml) and n-propylisocyanate (74 μL, 1.2 equivs). After two hours, solvent was removed and the crude residue was taken up in HCl/ethanol solution (1.2M, 15 ml) and stirred at 50^°C overnight. After solvent was removed, the crude 2,6-dimethyl-4-(3- propyl-ureido)-benzoic acid was isolated as a white solid (94 mg).[0425] ¹H NMR (CDCl₃) δ 0.83-0.99 (m, 7H), 1.02-1.11 (m, IH), 1.46-1.77 (m, 8H), 2.11 (s, 6H), 2.48-2.57 (m, IH), 1.66-1.82 (m, 3H), 3.12-3.22 (m, 3H), 3.52-3.20 (m, 4H), 3.75-3.82- 3.90 (m, IH), 4.11-4.25 (m, IH), 5.67-5.75 (m, IH), 6.61 (s, 2H), 6.89 (d, IH, J= 6 Hz), 7.03 (s, IH), 7.22 (s, IH), 7.27-7.32 (m, IH), 7.48 (s, IH), 8.87 (br s, IH); ES-MS m/z 573 (M+H).

References:

WO2006/138350,2006,A2 Location in patent:Page/Page column 196