Aniline → 2,6-dichloro-N-phenylpyridin-3-amine

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

The reaction was carried out under nitrogen. Two runs using the same amount of starting material (2,6-dichloro-3-iodopyridine (274 mg, 1 mmol)) and the same conditions were started and carried out as described in the following. BINAP (46.7 mg, 0.08 mmol) and Pd2(dba)3 (22.89 mg, 0.03 mmol) were given into a nitrogen charged reaction vessel and dissolved in dioxane (10ml). 2,6-dichloro-3-iodopyridine (274 mg, 1 mmol), aniline (0.457 ml, 5.00 mmol) and sodium tert-butoxide (144 mg, 1.50 mmol) were weight in another flask and flushed with nitrogen. The prepared ligand-Pd mixture was added and the reaction mixture was heated at 100°C over night. The reaction was monitored using TLC and LC/MS. After the reaction was completed, the dioxane was evapurated and both reaction vessels containing the same reaction-mixture were combined. The crude was solved in DCM, filtered through a silica plug and it followed a water work up using sodium bicarbonate (5 %), brine and water. The organic phase was dried over sodium sulfate and concentrated to yield a dark brown oil. NMR showed the desired product, as well as the bis-addition of aniline. The crude product was purified by reverse-phase preparative HPLC. Column: Kromasil C8. Eluent: A: MeCN, B: H2O/MeCN/CH3COOH, 95/5/0.2. Gradient: The A fraction was increased from 30 % to 70 % over 40 minutes. Flow: 70 mL/min. The relevant fractions (6-9) were concentrated and freeze dried to yield 220.3 mg (46%) a brown oil.

Herkunft & Nachweise