反応 #1017530

反応方程式

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

benzoyl isothiocyanate

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCl

N,N-diisopropylethylamine

NaHCO3

→

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

収率 82.5%

溶媒

MeCN

反応条件

後処理

1. 1
   workup.STIRRINGThe solution was stirred at rt for 2 h
2. 2
   抽出extracted with EtOAc (2×100 mL)
3. 3
   洗浄The combined extracts were washed with water (1×100 mL) and brine
4. 4
   乾燥dried (Na2SO4)
5. 5
   濃縮concentrated onto silica
6. 6
   その他Purification by silica gel chromatography (Gradient: 0.0 to 20% EtOAc/hexane)

実験手順

To a 150 mL round-bottomed flask was added (2S,4S)-4-amino-4-(6-bromo-3-fluoropyridin-2-yl)-1,1,1,5-tetrafluoropentan-2-ol (1.54 g, 4.41 mmol), MeCN (30 mL) and benzoyl isothiocyanate (Aldrich; 0.712 mL, 5.29 mmol). The reaction mixture was stirred at rt for 45 min and then 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCl (Oakwook Products, Inc.; 1.015 g, 5.29 mmol) and N,N-diisopropylethylamine (Aldrich; 1.54 mL, 8.82 mmol) were added. The solution was stirred at rt for 2 h and then treated with sat NaHCO3 and extracted with EtOAc (2×100 mL). The combined extracts were washed with water (1×100 mL) and brine and then dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (Gradient: 0.0 to 20% EtOAc/hexane) afforded N-((4S,6S)-4-(6-bromo-3-fluoropyridin-2-yl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (1.74 g, 3.64 mmol, 82% yield) as an off-white foam. MS m/z=480.0 [M+H]+. Calculated for C18H13BrF5N3O2: 479.0.

出典