Reacción #73840

Ecuación de reacción

Methanol

4-(4-Chloro-benzyl)-pyridine

bis-(2-chloro-ethyl)-carbamic acid tert-butyl ester

sodium hexamethyldisilazide

→

title compound

Rendimiento 0.7%

4-(4-Chloro-phenyl)-3,4,5,6-tetrahydro-2H-[4,4′]bipyridinyl-1-carboxylic acid tert-butyl ester

Rendimiento 0.7%

Disolventes

toluene

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato warm to room temperature
2. 2
   workup.STIRRINGstirred for a further 20 hours
3. 3
   Concentraciónthe mixture was concentrated in vacuo
4. 4
   Lavadowashed with 1N hydrochloric acid (×3) and brine
5. 5
   Secadodried (MgSO4)
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated
8. 8
   Otroto afford a residue which
9. 9
   Otrowas purified by column chromatography (SiO2)
10. 10
    Lavadoeluting with gradient of 2M methanolic ammonia in dichloromethane (1% to 5%)
11. 11
    OtroA second purification by column chromatography (SiO2)
12. 12
    Lavadoeluting with 50% ethyl acetate/petrol

Procedimiento

Under nitrogen, a solution of bis-(2-chloro-ethyl)-carbamic acid tert-butyl ester* (1.54 g, 6.36 mmol) in toluene (10 mL) was cooled in ice. 4-(4-Chloro-benzyl)-pyridine (1.30 g, 6.36 mmol) was added, followed over two minutes by sodium hexamethyldisilazide solution (10 mL, 20 mmol, 2M in THF). The mixture was stirred at 0° C. for 3.5 hours then allowed to warm to room temperature and stirred for a further 20 hours. Methanol was added then the mixture was concentrated in vacuo. The residue was taken up in ethyl acetate and washed with 1N hydrochloric acid (×3) and brine, dried (MgSO4), filtered and concentrated to afford a residue which was purified by column chromatography (SiO2), eluting with gradient of 2M methanolic ammonia in dichloromethane (1% to 5%). A second purification by column chromatography (SiO2), eluting with 50% ethyl acetate/petrol gave the title compound (16 mg, 0.7%). LCMS (PS-A2) Rt 2.65 min [M+H]+ 373.

Fuente