Reaktion #1909169

Reaktionsgleichung

1-methyl-piperidin-4-ol

sodium hydride

1-bromo-2,3-difluoro-benzene

→

4-(2-bromo-6-fluoro-phenoxy)-1-methyl-piperidine

Ausbeute 54.5%

Lösungsmittel

DMF

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITAfter 2 hr
2. 2
   Sonstige, partition the reaction mixture between water and ether
3. 3
   Trocknendry over anhydrous sodium sulfate
4. 4
   Sonstigeevaporate
5. 5
   Sonstigeto give a yellow oil
6. 6
   SonstigeSeparate on a silica gel column (110 g, solvent: ether, ether-2M NH3 in methanol 19:1, 9:1)

Vorschrift

Add slowly a solution of 1-methyl-piperidin-4-ol (2.98 g) in DMF (20 mL) into a suspension of sodium hydride (95%) (0.72 g) in DMF (25 mL) at room temperature. Heat the mixture in an oil bath at 65° C. After 30 min., add 1-bromo-2,3-difluoro-benzene (5.0 g) and stir at 65° C. After 2 hr., partition the reaction mixture between water and ether, dry over anhydrous sodium sulfate, and evaporate to give a yellow oil. Separate on a silica gel column (110 g, solvent: ether, ether-2M NH3 in methanol 19:1, 9:1) to obtain 4-(2-bromo-6-fluoro-phenoxy)-1-methyl-piperidine (4.06 g, 54% yield) and the title compound (1.60 g, 21% yield). Mass spectrum (electric spray) m/z=288 (M+1), 290 (M+2+1); 1H NMR (CDCl3): 7.12 (m, 1H), 6.92 (m, 2H), 4.30 (m, 1H), 2.69 (m, 2H), 2.30 (s, 3H), 2.28 (m, 2H), 1.97 (m, 2H), 1.89 (m, 2H).

Quelle