Reaktion #43563

Reaktionsgleichung

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

Ausbeute 41.0%

Lösungsmittel

hexane

EtOAc

CH2Cl2

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeUpon completion, there reaction
2. 2
   Sonstigewas evaporated
3. 3
   workup.ADDITIONis diluted with ethyl acetate (100 mL)
4. 4
   Extraktionextracted with 0.5M HCl (2×30 mL), saturated NaHCO3, and brine
5. 5
   TrocknenThe organic layer is dried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Sonstigeevaporated

Vorschrift

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.

Quelle