反应详情

温度

80 °C

[2-(4-fluoro-benzyl)-phenyl]-chloromethane (1 eq.), THF (1 L/mol), water (0.7 L/mol), Pd(OAc)2 (1.3 mol %), dppp (2.6 mol %) and sodium acetate (2.5 eq.) were placed in a inertized reactor. The reaction mixture is placed under a CO pressure of 4 bars and allowed to stir at 80° C. for 20 hours. The organic layer is separated and evaporated under pressure. Toluene (0.75 L/mol) is added to the residue and the carboxylic acid is extracted with a 2 N solution of sodium hydroxide (0.75 L/mol). The black particles of palladium are removed by filtration over Celite. The water layer is placed in a flask and acetic acid (0.9 L/mol) is added. The mixture is warmed up to 80° C. then allowed to spontaneously cool down. The crystallisation starts around 50° C. The crystals are filtered off at room temperature, washed with water and dried to give black [2-(4-fluoro-benzyl)-phenyl]-acetic acid (91%). Treatment of 5 g of black [2-(4-fluoro-benzyl)-phenyl]-acetic acid with charcoal in 25 ml of a mixture of acetic acid and water (7/3) allows the isolation of pure white crystals of [2-(4-fluoro-benzyl)-phenyl]-acetic acid. This step can be performed before the first addition of acetic acid.

1. customThe organic layer is separated
2. customevaporated under pressure
3. additionToluene (0.75 L/mol) is added to the residue
4. extractionthe carboxylic acid is extracted with a 2 N solution of sodium hydroxide (0.75 L/mol)
5. customThe black particles of palladium are removed by filtration over Celite
6. customThe water layer is placed in a flask
7. additionacetic acid (0.9 L/mol) is added
8. temperatureThe mixture is warmed up to 80° C.
9. temperatureto spontaneously cool down
10. customThe crystallisation
11. customstarts around 50° C
12. filtrationThe crystals are filtered off at room temperature
13. washwashed with water
14. customdried