反応 #43563

反応方程式

Diisopropylethylamine

2-(S)-(4-Fluoro-phenyl)-4-morpholin-4-yl-4-oxo-butyric acid

2-(S)-Amino-3-methyl-butan-1-ol

HATU

→

2-(S)-(4-Fluoro-phenyl)-N-(1-(S)-hydroxymethyl-2-methyl-propyl)-4-morpholin-4-yl-4-oxo-butyramide

収率 41.0%

溶媒

hexane

EtOAc

CH2Cl2

反応条件

後処理

1. 1
   その他Upon completion, there reaction
2. 2
   その他was evaporated
3. 3
   workup.ADDITIONis diluted with ethyl acetate (100 mL)
4. 4
   抽出extracted with 0.5M HCl (2×30 mL), saturated NaHCO3, and brine
5. 5
   乾燥The organic layer is dried over MgSO4
6. 6
   ろ過filtered
7. 7
   その他evaporated

実験手順

2-(S)-(4-Fluoro-phenyl)-4-morpholin-4-yl-4-oxo-butyric acid (2.00 g, 7.11 mmol, 1.0 eq.), 2-(S)-Amino-3-methyl-butan-1-ol (1.59 g, 7.33 mmol, 1.03 eq.) and HATU (2.41 g, 7.33 mmol, 1.03 mmol) were dissolved in CH2Cl2 and stirred at room temperature. Diisopropylethylamine (3.9 mL, 21.98 mmol, 3.1 eq.) was added via syringe and the reaction is monitored by LC/MS. Upon completion, there reaction was evaporated and is diluted with ethyl acetate (100 mL) and extracted with 0.5M HCl (2×30 mL), saturated NaHCO3, and brine. The organic layer is dried over MgSO4, filtered and evaporated. Column chromatography (0-100%) EtOAc in hexane gradient provided 2-(S)-(4-Fluoro-phenyl)-N-(1-(S)-hydroxymethyl-2-methyl-propyl)-4-morpholin-4-yl-4-oxo-butyramide as a clear oil (1.06 g, 2.89 mmol, 41%). HPLC-MS calcd. for C19H27FN2O4 (M+H+) 367.2, found 367.4; TLC (1:1 hexane/EtOAc) Rf=0.15.

出典