Reacción #674831

Ecuación de reacción

NH4Cl

1-benzylpiperidin-4-one

n-BuLi

2-bromo-5-fluoro-α,α-dimethyl-benzylalcohol

→

1-Benzyl-4-[4-fluoro-2-(1-hydroxy-1-methyl-ethyl)-phenyl]-4-hydroxypiperidine

Disolventes

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGThen, the resulting solution was stirred at r.t. overnight
3. 3
   ExtracciónThe resulting aqueous solution was extracted with DCM
4. 4
   OtroThe organic layer was separated
5. 5
   Concentraciónconcentrated in vacuo
6. 6
   OtroThe residue was purified by column chromatography (silica gel; heptane/EtOAc from 100/0 to 60/40 as eluent)
7. 7
   OtroThe desired fractions were collected
8. 8
   Concentraciónconcentrated in vacuo
9. 9
   Otroto yield intermediate D83 (0.4 g, 23%)

Procedimiento

To an anhydrous THF (50 mL) cooled at −70° C. stirred under nitrogen a 2.5 M solution of n-BuLi (4.22 mL, 10.54 mmol) was added. Then 2-bromo-5-fluoro-α,α-dimethyl-benzylalcohol (1.17 g, 5.02 mmol) [C.A.S.853271-16-6] was added dropwise. The resulting mixture was stirred at −70° C. for 2 h. Then a solution of 1-benzylpiperidin-4-one (1.33 g, 7.028 mmol) in anhydrous THF (10 ml) was added dropwise. Then, the resulting solution was stirred at r.t. overnight. The reaction mixture was poured into NH4Cl (aqueous sat. solution) at 5-10° C. The resulting aqueous solution was extracted with DCM. The organic layer was separated and concentrated in vacuo. The residue was purified by column chromatography (silica gel; heptane/EtOAc from 100/0 to 60/40 as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate D83 (0.4 g, 23%).

Fuente