| 68% |
Stage #1: methylamine With n-butyllithium In tetrahydrofuran at 0℃; for 1h;
Stage #2: 2-fluoro-4-bromobenzoic acid In tetrahydrofuran at -78℃; for 0.5h; |
13.1 Step 1: synthesis of compound 6.1
A solution of methylamine in tetrahydrofuran (2.0 M, 11 mL, 27.8 mmol) was dissolved in THF (10 mL) under ice-water bath, to the system was added n-butyllithium (8.2 mL, 20.5 mmol) dropwise. After the addition, the reaction was stirred at 0°C for 1h, and then the reaction system was cooled down to -78°C. To the system was added a solution of 4-bromo-2-fluorobenzoic acid (1.0 g, 4.57 mmol) in THF (5 mL), stirred at -78°C for 0.5h and quenched by addition of hydrochloric acid (1.0 M), extracted with ethyl acetate (5 mL × 3). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated to afford compound 6.1 (700 mg, yield: 68%) as a light-yellow solid. m/z: [M+H]+230 |
| 35% |
Stage #1: methylamine With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 1h;
Stage #2: 2-fluoro-4-bromobenzoic acid In tetrahydrofuran; hexane at -78℃; for 0.5h; |
150.1
Step 1 : To a solution of methylamine (2 M in THF, 128 mL, 255 mmol) in THF (23 mL) at 0 °C was added n-butyl lithium (2.5 M in hexanes, 80 mL, 201 mmol) slowly. The mixture was stirred for one hour at 0 °C and then it was transferred via cannula to a solution of 4-bromo-2- fluorobenzoic acid (5 g, 22.8 mmol) in THF (5 mL) at -78 °C. The reactio was stirred for 30 minutes before it was quenched at -78 °C with 270 mL of IN HCI. The aqueous layer was extracted ethyl acetate (4x200 mL) and the combined organic extracts were dried over Na2S04, filtered, and concentrated. The crude product was purified by flash chromatography (silica, eluent 100% CH2C12 to CH2Cl2/MeOH 93:7) to give 4-bromo-2- (methylamino)benzoic acid (1.83 g, 35%, LC-MS 94%) as a light orange solid. 1H NMR (400 MHz, CDCl3) <5 7.82 (d, J= 8.8 Hz, 1H), 6.86 (d, J= 1.2 Hz, 1H), 6.76 (dd, J= 1.6, 8.4 Hz, 1H), 2.94 (s, 3H); LC-MS m/z 230 [M]+. |
|
Stage #1: methylamine With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 1h;
Stage #2: 2-fluoro-4-bromobenzoic acid In tetrahydrofuran; hexane at -78℃; for 0.5h; |
150.1 Example 150
To a solution of methylamine (2 M in THF, 128 mL, 255 mmol) in THF (23 mL) at 0° C. was added n-butyl lithium (2.5 M in hexanes, 80 mL, 201 mmol) slowly. The mixture was stirred for one hour at 0° C. and then it was transferred via cannula to a solution of 4-bromo-2-fluorobenzoic acid (5 g, 22.8 mmol) in THF (5 mL) at -78° C. The reaction was stirred for 30 minutes before it was quenched at -78° C. with 270 mL of 1N HCl. The aqueous layer was extracted ethyl acetate (4*200 mL) and the combined organic extracts were dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash chromatography (silica, eluent 100% CH2Cl2 to CH2Cl2/MeOH 93:7) to give 4-bromo-2-(methylamino)benzoic acid (1.83 g, 35%, LC-MS 94%) as a light orange solid. 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J=8.8 Hz, 1H), 6.86 (d, J=1.2 Hz, 1H), 6.76 (dd, J=1.6, 8.4 Hz, 1H), 2.94 (s, 3H); LC-MS m/z 230 [M]+. |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
