Hydrochloric Acid → Capecitabine

温度

-2.5 °C

42.9 g of the compound obtained in Example 3 was added to 215 ml of methanol, and the mixture was stirred and cooled to −5 to 0° C. 10.8 g of NaOH was dissolved in 107 ml of water, and NaOH solution was added thereto while maintaining the reaction mixture temperature at less than 0° C. The resulting mixture was stirred for 30 min, and 48 ml of 6 N HCl was added dropwise thereto until the pH of the reaction mixture became 5.3. The resulting mixture was successively washed twice with 215 ml of dichloromethane and once with 108 ml of dichloromethane, and the combined organic layer was washed with 215 ml of water, dried over anhydrous sodium sulfate, filtered and concentrated under a reduced pressure. After adding 129 ml of ethylacetate thereto, the residue was mixed with 97 ml of ethylacetate by stirring to be crystallized. 97 ml of hexane was added dropwise thereto to allow the crystal to be matured, and the resulting mixture was stirred for 1 hr, cooled to 0° C. and again stirred for 1 hr. The resulting solid was filtered, washed with 86 ml of a solid mixture of ethylacetate and hexane (1:1 (v/v)) cooled to 0° C., and dried in a 35° C. vacuum oven overnight, to obtain 28.6 g of the title compound as a light white solid.

1. temperaturewhile maintaining the reaction mixture temperature at less than 0° C
2. stirringThe resulting mixture was stirred for 30 min
3. washThe resulting mixture was successively washed twice with 215 ml of dichloromethane and once with 108 ml of dichloromethane
4. washthe combined organic layer was washed with 215 ml of water
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under a reduced pressure
8. additionAfter adding 129 ml of ethylacetate
9. additionthe residue was mixed with 97 ml of ethylacetate
10. stirringby stirring
11. customto be crystallized
12. addition97 ml of hexane was added dropwise
13. stirringthe resulting mixture was stirred for 1 hr
14. temperaturecooled to 0° C.
15. stirringagain stirred for 1 hr
16. filtrationThe resulting solid was filtered
17. washwashed with 86 ml of a solid mixture of ethylacetate and hexane (1:1 (v/v))
18. temperaturecooled to 0° C.
19. customdried in a 35° C. vacuum oven overnight

ORDレコード

ord-b8a47c24f9f24618bd9e6669282b15e1

出典データセット

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08097706B2