تفاعل #344090

معادلة التفاعل

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

المردود 20.0%

المذيبات

tetrahydrofuran

ether

tetrahydrofuran

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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.

المصدر