Reaktion #330
ord-724091f002d04d2ea6bfe923f45ebf01
Reaktionsgleichung
Lösungsmittel
Reaktionsbedingungen
Vorschrift
**Purpose:** Buchwald-Hartwig coupling using unpurified ethyl 4-bromobenzofuran-2-carboxylate. The analysis on crude 4-bromobenzofuran-2-carboxylate shows traces of non cyclized and non aromoatized by-products. 2010-03-02 15:25:22: To a 25 mL roundbottomed flask was added ethyl 4-bromobenzofuran-2-carboxylate (LR; 1 g; 3.72 mmol) and toluene (7 mL/g-bulk- LR; 7 mL). The mixture was concentrated under reduced pressure. To the mixture was added toluene (7 mL/g-bulk-LR; 7 mL) and the mixture was concentrated a second time under reduced pressure. To the mixture was added toluene (7 mL/g-bulk-LR; 7 mL) followed by 1-benzylpiperazine (1.3 eq; 0.852 g; 0.84 mL), BINAP (0.04 eq; 93 mg) and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.02 eq; 68 mg). The mixture was stirred for 5 minutes followed by addition of POTASSIUM TERT-BUTOXIDE (1.4 eq; 0.58 g). The mixture is stirred at Tm=50 °C. 15:45:57: IPC1 (15 min) sample was gathered. The sample was quenched with a mixture consisting of 700 mM acetic acid buffer pH=2 and methanol. The sample was filtered and analyzed by means of HPLC-UV (EN03690-30-001-F) which indicated 44 % conversion 17:09:21: IPC2 (100 min) sample was gathered. The sample was quenched with a mixture consisting of 700 mM acetic acid buffer pH=2 and methanol. The sample was filtered and analyzed by means of HPLC-UV (EN03690-30-001-H) which indicated 95 % conversion. 17:20:00: The temperature was allowed to reach rt and the mixture was stirred over night. 2010-03-03 09:51:29: IPC3 (18 h) sample was gathered. The sample was quenched with a mixture consisting of 700 mM acetic acid buffer pH=2 and methanol. The sample was filtered and analyzed by means of HPLC-UV (EN03690-30-001-J) which indicated +99 % conversion. 10:10:32: The mixture was transfered to a mixture consisting of 700 mM acetate buffer pH=2 (12.5 mL/g-bulk-LR; 12.5 mL) and isopropyl acetate (6.2 mL/g-bulk- LR; 6.2 mL) to give pH=5.65. To the mixture was added 4 M aqueous sulfuric acid (1.77 mL/g-bulk-LR; 1.77 mL) to give pH=2. The mixture was stirred for 15 minutes. The phases were separated and analyzed by means of HPLC-UV 12:32:57: To the water phase was added dichloromethane (10 mL/g-bulk-LR; 10 mL). The mixture was stirred and 50 % aqueous sodium hydroxide (1 mL) was added to give pH=12. The phases were separated and analyzed by means of HPLC- UV. The organic phase was concentrated under reduced pressure to give yellow oil. The crude product was purified by means of column chromatography (40 g SiO2; 4 % MeOH, 1 NH3 in MeOH in DCM; Rf=0.2). Yellow solid was obtained (250 mg). 1H NMR showed not correct product. **Result:** Correct product was not isolated.