反应详情

Methyl 4-bromomethyl-2,6-diacetoxybenzoate (45.8 grams, 133 mmoles) was dissolved in N,N-dimethylformamide (150 mL), and sodium azide (8.8 g, 135 mmoles) was added. The reaction mixture was stirred for 6 hours at room temperature. Dichloromethane (350 mL) was added to the reaction mixture, and this solution was washed with water (250 mL), 1M aqueous hydrochloric acid (250 mL), and saturated aqueous sodium chloride (150 mL). The organic solution was dried over anhydrous magnesium sulfate, filtered, and evaporated to a clear, pale yellow oil. The oil was dissolved in methanol (750 mL) and transferred to a 2 L Parr hydrogenation flask. Palladium on carbon catalyst (10% [w/w], 1.5 g) in water (10 mL) was added, followed by concentrated hydrochloric acid (15 mL). The flask was affixed to a Parr hydrogenator, and the mixture was shaken at room temperature under 30 psi of hydrogen for 24 hours. The reaction mixture was filtered through a 0.45 mm nylon filter. The retained solid was then washed with methanol (150 mL), and concentrated hydrochloric acid (7 mL) was added to the filtrate. The filtrate was heated to reflux for 2 hours, cooled to room temperature, and evaporated to dryness to give an off-white solid. This solid was dissolved in hot denatured ethanol (250 mL) and the solution was allowed to cool to room temperature. White crystals formed quickly. The mixture was then chilled for 16-18 hours at 4° C. to complete crystallization. The solid was filtered, washed with a little cold ethanol (50 mL) and then diethyl ether (150 mL), and dried in vacuo over potassium hydroxide pellets to afford 16.0 grams (52% yield based on monobromo starting material) of methyl 4-aminomethyl-2,6-dihydroxybenzoate hydrochloride (m.p. >260° C., open capillary, uncorrected).

1. washthis solution was washed with water (250 mL), 1M aqueous hydrochloric acid (250 mL), and saturated aqueous sodium chloride (150 mL)
2. dry with materialThe organic solution was dried over anhydrous magnesium sulfate
3. filtrationfiltered
4. customevaporated to a clear, pale yellow oil
5. dissolutionThe oil was dissolved in methanol (750 mL)
6. additionPalladium on carbon catalyst (10% [w/w], 1.5 g) in water (10 mL) was added
7. stirringthe mixture was shaken at room temperature under 30 psi of hydrogen for 24 hours
8. filtrationThe reaction mixture was filtered through a 0.45 mm nylon
9. filtrationfilter
10. washThe retained solid was then washed with methanol (150 mL), and concentrated hydrochloric acid (7 mL)
11. additionwas added to the filtrate
12. temperatureThe filtrate was heated
13. temperatureto reflux for 2 hours
14. temperaturecooled to room temperature
15. customevaporated to dryness
16. customto give an off-white solid
17. temperatureto cool to room temperature
18. customWhite crystals formed quickly
19. temperatureThe mixture was then chilled for 16-18 hours at 4° C.
20. customcrystallization
21. filtrationThe solid was filtered
22. washwashed with a little cold ethanol (50 mL)
23. dry with materialdiethyl ether (150 mL), and dried in vacuo over potassium hydroxide pellets