Reaktion #539482

Reaktionsgleichung

tert-butyl 4-(4-(hydroxymethyl)phenyl)piperazine-1-carboxylate

triphenylphosphine

2-fluoroethanol

diisopropylazodicarboxylate

→

tert-butyl 4-(4-((2-fluoroethoxy)methyl)phenyl)piperazine-1carboxylate

Ausbeute 22.6%

Lösungsmittel

water

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Extraktionextracted with EtOAc (2×10 mL)
2. 2
   WaschenThe combined organic layers were washed with water (20 mL) and brine (20 mL)
3. 3
   Trocknendried over Na2SO4
4. 4
   Einengenconcentrated
5. 5
   Sonstigeto obtain a crude oil
6. 6
   SonstigePurification of the crude material

Vorschrift

To a solution of tert-butyl 4-(4-(hydroxymethyl)phenyl)piperazine-1-carboxylate (100 mg, 0.34 mmol) in THF (1 mL) was added triphenylphosphine (135 mg, 0.51 mmol), 2-fluoroethanol (24 μL, 0.41 mmol) and diisopropylazodicarboxylate (99 μL, 0.51 mmol). The reaction mixture stirred at room temperature overnight. The next day the reaction mixture was diluted with water (5 mL) and extracted with EtOAc (2×10 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL), dried over Na2SO4, and concentrated to obtain a crude oil. Purification of the crude material using silica gel chromatography (gradient of 0% to 100% EtOAc in hexanes) afforded tert-butyl 4-(4-((2-fluoroethoxy)methyl)phenyl)piperazine-1carboxylate as a colorless oil (26 mg, 22% yield). 1H NMR (300 MHz, CDCl3) δ 7.27 (d, 2H, J=9.0 Hz), 6.89 (d, 2H, J=9.0 Hz), 4.65 (m, 1H), 4.52 (s, 2H), 4.49 (m, 1H), 3.74 (m, 1H), 3.64 (m, 1H), 3.58 (dd, 4H, J=6.0, 3.0 Hz), 3.13 (dd, 4H, J=6.0, 3.0 Hz), 1.49 (s, 9H); 19F NMR (282.4 MHz, CDCl3): δ−223.01 (m, 1F); 13C NMR (75.5 MHz, CDCl3); δ 154.7, 150.9, 129.4, 129.2, 116.5, 84.3 (82.0), 79.9, 73.0, 68.8 (68.7), 49.3, 44.0, 28.4; HRMS calcd for C18H27FN2O5: 339.20785 found 339.20790.

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