Reacción #2275682

Ecuación de reacción

1-(2-clorophenyl)-3-methylisoquinoline

1-(2-chlorophenyl)-3-methylisoquinoline

N-bromo-succinimide

benzoyl peroxide

1-(2-clorophenyl)-3-isoquinolinecarboxylic acid

→

1-(2-clorophenyl)-3-isoquinolinecarboxaldehyde

Disolventes

CCl4

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturawas heated
2. 2
   Temperaturato reflux
3. 3
   Otrowhile being illuminated by a flood lamp for 5 hours
4. 4
   Filtraciónfiltered
5. 5
   LavadoThe filtrate was washed with saturated NaHCO3 (1×40 mL)
6. 6
   Secadodried with Na3SO4
7. 7
   Filtraciónfiltered
8. 8
   Concentraciónconcentrated in vacuo
9. 9
   workup.ADDITION(10.13 g) in EtOH (140 mL) and THF (70 mL) was added dropwise a solution of AgNO3 (10.595 g) in H2O (6 mL)
10. 10
    TemperaturaThe mixture was refluxed for 1 hour
11. 11
    Filtraciónfiltered hot
12. 12
    LavadoThe filter cake was washed with hot THF (2×20)
13. 13
    ConcentraciónThe combined filtrate was concentrated in vacuo

Procedimiento

Then 1-(2-clorophenyl)-3-isoquinolinecarboxylic acid 81 is formed by the following process. A mixture of 1-(2-clorophenyl)-3-methylisoquinoline 77 (6.68 g, 19.88 mmol), N-bromo-succinimide (NBS) (8.896 g, 19.98 mmol), and benzoyl peroxide (BPO) (0.57 g) in CCl4 was heated to reflux while being illuminated by a flood lamp for 5 hours. The reaction was cooled to room temperature and filtered. The filtrate was washed with saturated NaHCO3 (1×40 mL), dried with Na3SO4, filtered and concentrated in vacuo. The crude dibromide yellow product 79 was used in the next step. To a refluxing solution of the crude dibromide 79. (10.13 g) in EtOH (140 mL) and THF (70 mL) was added dropwise a solution of AgNO3 (10.595 g) in H2O (6 mL). The mixture was refluxed for 1 hour and filtered hot. The filter cake was washed with hot THF (2×20). The combined filtrate was concentrated in vacuo to give crude 1-(2-clorophenyl)-3-isoquinolinecarboxaldehyde as a dark yellow oil. (9 g) This oil was used without purification. To a solution of the crude aldehyde in absolute EtOH (100 mL) was slowly added a solution of AgNO3 (11.11 g) in 10 mL H2O. to this stirred solution was added dropwise a solution of NaOH (9.43 g) in H2O (140 mL). The resulting black slurry was stirred at room temperature for 2 hours. The solution was then filtered through a Celite column. The filter cake was washed with ether. The ether was evaporated and the aqueous solution was made slightly acidic with concentrated HCl. The precipitate was collected by filtration, then washed with H2O. It was then recrystallized from CH3CN affording pale yellow crystals (2.63 g, 35%).

Fuente