反応 #1017542

反応方程式

(2S,4R)-4-amino-4-(6-bromo-3-fluoropyridin-2-yl)-1,1,1,5,5-pentafluoropentan-2-ol

benzoyl isothiocyanate

triethylamine

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

→

N-((4R,6S)-4-(6-bromo-3-fluoropyridin-2-yl)-4-(difluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide

収率 74.0%

溶媒

THF

water

反応条件

後処理

1. 1
   温度The mixture was heated at 75° C. for 1.5 h
2. 2
   温度to cool to RT
3. 3
   抽出extracted with EtOAc
4. 4
   抽出The organic extract
5. 5
   洗浄was washed with satd NaCl (10 mL)
6. 6
   乾燥dried over MgSO4
7. 7
   ろ過The solution was filtered
8. 8
   濃縮concentrated in vacuo
9. 9
   その他The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
10. 10
    洗浄eluting with a gradient of 0% to 30% EtOAc in hexane

実験手順

To a 50-mL round-bottomed flask was added (2S,4R)-4-amino-4-(6-bromo-3-fluoropyridin-2-yl)-1,1,1,5,5-pentafluoropentan-2-ol (22 mg, 0.060 mmol) and benzoyl isothiocyanate (8.87 μl, 0.066 mmol) in THF (599 μl). The reaction mixture was stirred at RT for 16 h. To the reaction mixture was added triethylamine (10.00 μl, 0.072 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (12.64 mg, 0.066 mmol). The mixture was heated at 75° C. for 1.5 h. The reaction mixture was allowed to cool to RT and was diluted with water and extracted with EtOAc. The organic extract was washed with satd NaCl (10 mL) and dried over MgSO4. The solution was filtered and concentrated in vacuo. The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 30% EtOAc in hexane, to provide N-((4R,6S)-4-(6-bromo-3-fluoropyridin-2-yl)-4-(difluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (22 mg, 0.044 mmol, 74.0% yield) as off-white solid. MS m/z=496, 498 M+, Calculated for C18H12BrF6N3O2: 496.20.

出典