Reacción #62049

Ecuación de reacción

NaHCO3 EtOAc

1-propylphosphonic acid cyclic anhydride

2-methoxy-5,6,7,8-tetrahydroquinoline

t-BuLi

CO2

N-[4-(dimethylamino)benzyl]4-isopropylaniline

DMF

4-methylmorpholine

→

title compound

(+/−)-N-[4-(Dimethylamino)benzyl]-N-(4-isopropylphenyl)-2-methoxy-5,6,7,8-tetrahydroquinoline-8-carboxamide

Disolventes

Et2O

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe reaction
2. 2
   Temperaturato warm to room temperature
3. 3
   Otrothe solvent was removed by the flow of CO2
4. 4
   Otrothe reaction
5. 5
   Temperaturato warm to room temperature overnight
6. 6
   workup.ADDITIONthis mixture was poured into a separatory funnel
7. 7
   LavadoThe organic layer was washed with brine
8. 8
   Secadodried over anhydrous MgSO4
9. 9
   Filtraciónfiltered
10. 10
    Concentraciónconcentrated
11. 11
    OtroThe crude material was further purified by flash chromatography
12. 12
    Lavadoeluting with a gradient from 100% hexanes to 25% EtOAc/hexanes

Procedimiento

To a 0.22 M solution of 2-methoxy-5,6,7,8-tetrahydroquinoline in Et2O at −78° C. was added 1.7 equiv of t-BuLi [1,7M] over 5 min. After allowing the reaction to warm up to 0° C. and stirring at this temperature for 30 min, a stream of CO2(g) was then allowed to flow into the flask. The final mixture was allowed to warm to room temperature and the solvent was removed by the flow of CO2. To a solution/suspension of the resulting crude lithium carboxylate salt in DMF (12 equiv) at 0° C. was successively added 1.2 equiv of N-[4-(dimethylamino)benzyl]4-isopropylaniline, 12 equiv of 4-methylmorpholine and 4.0 equiv of 1-propylphosphonic acid cyclic anhydride (50% in EtOAc). After allowing the reaction to warm to room temperature overnight, this mixture was poured into a separatory funnel containing aqueous NaHCO3/EtOAc. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered and concentrated. The crude material was further purified by flash chromatography, eluting with a gradient from 100% hexanes to 25% EtOAc/hexanes to provide the title compound as a white solid.

Fuente