反应详情

温度

110 °C

A 5 L three-necked round-bottomed flask equipped with a reflux condenser connected to a base trap, a glass rod air driven stirrer, and a thermometer was charged with 192.0 g (0.946 mmol) of (±)-3-(4'-methoxybenzoyl)-3-methylpropionitrile from Example G and 48% aqueous hydrogen bromide (1.0 L). The reaction mixture was heated over 1 hr to 65° C. then stirred at this temperature for 45 min (this effected complete hydrolysis of the nitrile moiety). The reaction temperature was increased to 110° C. and the solution was stirred for 3.5 hrs to effect demethylation. The solution was cooled to 23° C., diluted with water (1250 ml), cooled to 0° C. and the pH was adjusted to pH 8.5 with sodium hydroxide pellets (325 g) and powdered sodium bicarbonate (50 g). The aqueous solution was washed with EtOAc (2.5 L), transferred to a 4 L beaker in an ice/water bath and the pH was adjusted to pH 2 with 36% concentrated hydrochloric acid (Fisher, 150 ml). The aqueous solution was extracted with EtOAc (1L) and the organic layer was separated. The aqueous solution was saturated with solid sodium chloride (200 g) then extracted again twice with EtOAc (1×1L, 1×0.5L). The combined organic extracts were dried over anhydrous magnesium sulfate (10 g), filtered and concentrated in vacuo to provide 154.0 g (78%) of pure (±)-3-(4'-hydroxybenzoyl)-3-methylpropanoic acid, m.p. 122°-126° C.

1. customA 5 L three-necked round-bottomed flask equipped with a reflux condenser
2. customconnected to a base trap
3. temperatureThe reaction mixture was heated over 1 hr to 65° C.
4. stirringthe solution was stirred for 3.5 hrs
5. temperatureThe solution was cooled to 23° C.
6. temperaturecooled to 0° C.
7. washThe aqueous solution was washed with EtOAc (2.5 L)
8. customtransferred to a 4 L beaker in an ice/water bath
9. extractionThe aqueous solution was extracted with EtOAc (1L)
10. customthe organic layer was separated
11. extractionthen extracted again twice with EtOAc (1×1L, 1×0.5L)
12. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate (10 g)
13. filtrationfiltered
14. concentrationconcentrated in vacuo