Reaktion #2349693

Reaktionsgleichung

(4-Methyl-morpholin-3-yl)-methanol

NaH

4-(2,4-Difluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester

Intermediate 12

4-(2,4-Difluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester

→

(4-methylmorpholin-3-yl)methyl 4-(2,4-difluorophenyl)piperazine-1-carboxylate

Ausbeute 19.0%

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe reaction mixture was stirred at room temperature overnight
2. 2
   SonstigeThe reaction mixture was quenched with the addition of aqueous NaHCO3 (0.5 mL) at 0° C
3. 3
   workup.STIRRINGThe reaction mixture was stirred for 1 h
4. 4
   Sonstigethe solvents were removed in vacuo
5. 5
   ExtraktionThe aqueous phase was extracted with EtOAc (×3)
6. 6
   WaschenThe combined organic layers were washed with aqueous Na2CO3
7. 7
   Trocknendried (MgSO4)
8. 8
   Sonstigethe solvent removed in vacuo
9. 9
   SonstigeThe residue was purified by column chromatography (normal phase, Apollo silica, 1% MeOH in DCM)
10. 10
    Sonstigethe solvents were removed in vacuo

Vorschrift

(4-Methyl-morpholin-3-yl)-methanol (387 mg, 2.95 mmol) in THF (7.5 mL) was added dropwise to a suspension of NaH (60% dispersion in oil, prewashed with hexane; 354 mg, 8.85 mmol) in anhydrous THF (7.5 mL) at 0° C. and stirred under nitrogen for 40 minutes. 4-(2,4-Difluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester (Intermediate 12; 1.28 g, 3.54 mmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with the addition of aqueous NaHCO3 (0.5 mL) at 0° C. The reaction mixture was stirred for 1 h and then the solvents were removed in vacuo. The residue was suspended between water and EtOAc. The aqueous phase was extracted with EtOAc (×3). The combined organic layers were washed with aqueous Na2CO3, dried (MgSO4) and the solvent removed in vacuo. The residue was purified by column chromatography (normal phase, Apollo silica, 1% MeOH in DCM) and the solvents were removed in vacuo to give (4-methylmorpholin-3-yl)methyl 4-(2,4-difluorophenyl)piperazine-1-carboxylate (197 mg, 19%) as a colourless oil.

Quelle