反应详情

A 500 ml round-bottomed flask was charged with methanol (200 ml) and 1 N NaOH (194 ml, 194 mmol, approximately 1.36 equivalents relative to input dichloro-(3-hydroxy-adamantan-1-yl)-acetic acid methyl ester (Formula VIII)). The resulting solution was cooled in an ice bath until the temperature was <9° C. The cold bath was removed and dichloro-(3-hydroxy-adamantan-1-yl)-acetic acid methyl ester (Formula VIII)(41.68 g, 142.1 mmol) was added. The resulting suspension was allowed to stir at ambient temperature under argon. After stirring for approximately 6 hours, an additional portion of methanol (10 ml) was used to rinse down the vessel walls. After stirring for approximately 17 hours, the reaction mixture was filtered to remove a small amount of particulate material. The resulting solution was transferred to a 2-liter three-necked flask equipped with a mechanical stirrer. Water (900 ml) was used to dilute the reaction mixture and to compete the transfer. The resulting solution was acidified by the addition of concentrated HCl (38 ml, approximately 456 mmol). A white solid quickly formed. The mixture was gently stirred for approximately 20 minutes and then placed in an ice bath. After gently stirring for approximately 90 minutes, the stirrer was stopped and the mixture was allowed to stand in the ice bath for an additional 2 hours. The resulting suspension was filtered and the filtercake was washed with ice cold water. The bulk of the water was removed from the solid by pulling air through the filtercake. The material was then dried under vacuum at ambient temperature for 22 hours to give dichloro-(3-hydroxy-adamantan-1-yl)-acetic acid (Formula IX) as a colorless powdery solid: 39.19 grams (98.7% yield); mp 238° C. (dec).

1. temperatureThe resulting solution was cooled in an ice bath until the temperature
2. customwas <9° C
3. customThe cold bath was removed
4. stirringAfter stirring for approximately 6 hours
5. washto rinse down the vessel walls
6. stirringAfter stirring for approximately 17 hours
7. filtrationthe reaction mixture was filtered
8. customto remove a small amount of particulate material
9. customThe resulting solution was transferred to a 2-liter three-necked flask
10. customequipped with a mechanical stirrer
11. additionto dilute the reaction mixture
12. customA white solid quickly formed
13. stirringThe mixture was gently stirred for approximately 20 minutes
14. customplaced in an ice bath
15. stirringAfter gently stirring for approximately 90 minutes
16. filtrationThe resulting suspension was filtered
17. washthe filtercake was washed with ice cold water
18. customThe bulk of the water was removed from the solid
19. customThe material was then dried under vacuum at ambient temperature for 22 hours