反应详情

To a stirred cooled (−10° C.) mixture of lithium aluminum hydride (2.46 g, 65 mmol) and dry THF (50 mL) was added dropwise a solution of 3-(3,4-difluorophenyl)4-(ethoxycarbonylamino)-1-butanol (8.85 g, 32.4 mmol) in THF (40 mL). The solution was heated under reflux for 1.25 h, cooled (ice bath) and saturated sodium sulfate (150 mL) solution was added dropwise. The mixture was stirred at room temperature for 1 hr, filtered through diatomaceous earth, washed with THF and the solvent removed in vacuo. The residue was dissolved in DCM, washed with water, dried (Na2SO4), filtered and the solvent removed in vacuo. Purification by chromatography (2-5% and 10% methanol in DCM) provided the title compound (5.20 g, 75%) as a pale green oil. 1H-NMR (CDCl3) δ 1.85-1.96 (m, 2H, CH) 2.45 (s, 3H, CH3) 2.74-2.85 (m, 3H, CH) 3.37 (br s, 2H, NH, OH) 3.50-3.58 (m, 1H, CH) 3.66-3.73, m, 1H, CH), 6.87-7.35 (m, 3H, ArH). MS m/z 216 (M+H).

1. temperatureTo a stirred cooled
2. temperatureThe solution was heated
3. temperatureunder reflux for 1.25 h
4. additionwas added dropwise
5. filtrationfiltered through diatomaceous earth
6. washwashed with THF
7. customthe solvent removed in vacuo
8. dissolutionThe residue was dissolved in DCM
9. washwashed with water
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. customthe solvent removed in vacuo
13. customPurification by chromatography (2-5% and 10% methanol in DCM)