Reacción #10301

Ecuación de reacción

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

Rendimiento 6.6%

Disolventes

EtOAc

2-butanone

diethyl ether

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturawas heated
2. 2
   Temperaturaat reflux for 5 h under an inert atmosphere
3. 3
   OtroThe cooled reaction mixture
4. 4
   Otrowas partitioned between EtOAc and water
5. 5
   LavadoThe EtOAc extracts were washed with water and saturated brine
6. 6
   Secadothen dried (MgSO4)
7. 7
   Filtraciónfiltered
8. 8
   Concentraciónconcentrated in vacuo
9. 9
   OtroThe resultant material was purified by column chromatography on silica
10. 10
    Lavadoeluted with a gradient of 0–15% MeOH-EtOAc
11. 11
    Otroto give the free base
12. 12
    OtroThe solvents was removed in vacuo

Procedimiento

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)+.

Fuente