反应详情

温度

0 °C

To a stirred solution of (viii) (3.0 g, 8.8 mmol) in DCM (90 ml) was added DIPEA (5.4 mL, 30.8 mmol.) and the reaction mixture cooled to 0° C. Methanesulfonyl chloride (1.70 mL, 22.0 mmol) was added dropwise and the reaction stirred for 2 h. Water (100 mL) was then added to the reaction and pH of the aqueous layer adjusted to pH˜5 using aq. 2N HCl. The organics were separated and the aqueous layer was extracted into EtOAc (2×100 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo. A portion of the solid obtained (2.6 g) was dissolved in EtOH (166 mL), solid potassium hydroxide (2.82 g, 50.3 mmol) was added and the reaction heated at 50° C. After 2 h, the reaction mixture was cooled to RT, diluted with water (100 mL) and the pH adjusted to 5 using aq. 2N HCl. The organics were extracted into EtOAc (3×100 mL), dried (Na2SO4) and concentrated in vacuo to give 4 g crude of the desired product. A portion of the crude material (1 g) was purified by column chromatography on silica gel eluting with EtOAc:n-hexane (gradient elution from 10% to 40% v/v) to give Compound (1) (330 mg). ESI-MS m/z calculated for [M+H]+: 419.1. found: 419.1. 1H NMR (400 MHz, d6-Acetone) δ 7.79 (brs, 1H), 7.66 (s, 1H), 7.61 (brs, 1H), 7.56-7.51 (m, 2H), 7.49 (s, 1H), 7.46-7.41 (m, 2H), 3.02 (s, 3H), 2.81 (d, J=4.7 Hz, 3H), 2.11-2.01 (m, 1H), 0.96-0.90 (m, 2H), 0.66-0.59 (m, 2H).

1. customThe organics were separated
2. extractionthe aqueous layer was extracted into EtOAc (2×100 mL)
3. dry with materialThe combined organics were dried (Na2SO4)
4. concentrationconcentrated in vacuo
5. customA portion of the solid obtained (2.6 g)
6. temperaturethe reaction heated at 50° C
7. waitAfter 2 h
8. temperaturethe reaction mixture was cooled to RT
9. extractionThe organics were extracted into EtOAc (3×100 mL)
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated in vacuo