Reaktion #10301

Reaktionsgleichung

3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine hydrochloride

potassium carbonate

sodium iodide

4-chloro-1-(4-fluorophenyl)butan-1-one

HCl

→

1-(4-fluorophenyl)-4-(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)butan-1-one hydrochloride

Ausbeute 6.6%

Lösungsmittel

EtOAc

2-butanone

diethyl ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas heated
2. 2
   Temperaturat reflux for 5 h under an inert atmosphere
3. 3
   SonstigeThe cooled reaction mixture
4. 4
   Sonstigewas partitioned between EtOAc and water
5. 5
   WaschenThe EtOAc extracts were washed with water and saturated brine
6. 6
   Trocknenthen dried (MgSO4)
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated in vacuo
9. 9
   SonstigeThe resultant material was purified by column chromatography on silica
10. 10
    Wascheneluted with a gradient of 0–15% MeOH-EtOAc
11. 11
    Sonstigeto give the free base
12. 12
    SonstigeThe solvents was removed in vacuo

Vorschrift

A stirred mixture of 3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine hydrochloride (150 mg, 0.56 mmol), 2-butanone (5 mL), potassium carbonate (0.25 g, 1.81 mmol), sodium iodide (20 mg, 0.13 mmol) and 4-chloro-1-(4-fluorophenyl)butan-1-one (115 μL, 0.68 mmol) was heated at reflux for 5 h under an inert atmosphere. The cooled reaction mixture was partitioned between EtOAc and water. The EtOAc extracts were washed with water and saturated brine then dried (MgSO4), filtered and concentrated in vacuo. The resultant material was purified by column chromatography on silica eluted with a gradient of 0–15% MeOH-EtOAc to give the free base. This was dissolved in EtOAc and treated with 1M HCl in diethyl ether. The solvents was removed in vacuo to give 1-(4-fluorophenyl)-4-(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)butan-1-one hydrochloride as a white solid (16 mg). 1H NMR (400 MHz, CD3OD) δ 1.90–1.99 (2H, m), 3.17 (2H, t, J=6.6 Hz), 3.25–3.35 (3H, m), 3.68 (2H, d, J=7.3 Hz), 4.0–4.2 (2H, br s), 4.2–4.4 (2H, br s), 7.20–7.27 (2H, m), 7.39–7.46 (2H, m), 7.98–8.04 (2H, m), 8.05–8.10 (2H, m). m/z (ES+) 394 (M+H)+.

Quelle