Reacción #344090

Ecuación de reacción

ammonium chloride

2-[(2-fluorophenyl)(1-(ethoxy)ethoxy)methyl]-3-thiophenecarboxaldehyde

N-methyl-4-chloropiperidine

N-methyl-4-piperidinylmagnesium chloride

→

α-[2-[2-fluorophenyl(1-(ethoxy)ethoxy)methyl]-3-thienyl]-1-methyl-4-piperidinemethanol

Rendimiento 20.0%

Disolventes

tetrahydrofuran

ether

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas added, via syringe
2. 2
   OtroThe layers were separated
3. 3
   Lavadothe organic layer washed with water
4. 4
   ExtracciónThe combined aqueous layers were back-extracted with ether
5. 5
   Lavadothe combined organic layers washed with brine
6. 6
   Secadodried over anhydrous potassium carbonate
7. 7
   Filtraciónfiltered
8. 8
   Concentraciónconcentrated
9. 9
   OtroThe residue was purified by flash column chromatography (silica gel, 0-45% methanol/dichloromethane)

Procedimiento

To a stirred solution of the 2-[(2-fluorophenyl)(1-(ethoxy)ethoxy)methyl]-3-thiophenecarboxaldehyde and tetrahydrofuran (400 ml), cooled to -78° C. under nitrogen, was added, via syringe, N-methyl-4-piperidinylmagnesium chloride over 1.5 hrs. (the Grignard reagent was prepared from N-methyl-4-chloropiperidine (29.4 g) according to the procedure of J. T. Strupczewski, et al., et al., J. Med. Chem., 28, 761 (1985), followed by dilution with tetrahydrofuran (45 ml)). The solution was allowed to warm slowly to -20° C. over 2.5 hrs, and dilute aqueous ammonium chloride solution and ether were added. The layers were separated and the organic layer washed with water. The combined aqueous layers were back-extracted with ether, and the combined organic layers washed with brine, dried over anhydrous potassium carbonate, filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 0-45% methanol/dichloromethane) to afford 6.4 g (20% overall) of α-[2-[2-fluorophenyl(1-(ethoxy)ethoxy)methyl]-3-thienyl]-1-methyl-4-piperidinemethanol.

Fuente