反応 #344090

反応方程式

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

収率 20.0%

溶媒

tetrahydrofuran

ether

tetrahydrofuran

反応条件

後処理

1. 1
   workup.ADDITIONwas added, via syringe
2. 2
   その他The layers were separated
3. 3
   洗浄the organic layer washed with water
4. 4
   抽出The combined aqueous layers were back-extracted with ether
5. 5
   洗浄the combined organic layers washed with brine
6. 6
   乾燥dried over anhydrous potassium carbonate
7. 7
   ろ過filtered
8. 8
   濃縮concentrated
9. 9
   その他The residue was purified by flash column chromatography (silica gel, 0-45% methanol/dichloromethane)

実験手順

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.

出典