反应详情

温度

20 °C

The process is performed under the conditions of Example 2, starting with 12.45 g of tert-butyl (1R)-1-(4-methoxyphenyl)-2-hydroxyethylcarbamate in 130 cm3 of 2.5N hydrochloric methanol, with stirring for 1 h 30 minutes at a temperature in the region of 20° C., and then for 30 minutes at a temperature in the region of 30° C. The reaction mass is evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. 61 cm3 of aqueous 5% sodium hydrogen carbonate solution are added to the residue obtained and the mixture is then extracted with 3 times 100 cm3 of dichloromethane. The aqueous phase is separated out after settling has taken place and is then evaporated as above. The solid obtained is taken up in 65 cm3 of aqueous 1N sodium hydroxide solution and the resulting solution is reduced to ⅔ of its volume by concentration under the above conditions. The mixture is extracted with 3 times 100 cm3 of dichloromethane. The extracts are combined, dried over magnesium sulfate, filtered and evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The crystals obtained are dried under reduced pressure (5 kPa) at about 20° C. 5.86 g of (2R)-2-amino-2-(4-methoxyphenyl)-1-ethanol are obtained in the form of a white solid melting at 103° C. tert-Butyl (1R)-1-(4-methoxyphenyl)-2-hydroxyethylcarbamate: The process is performed under the conditions of Example 2, starting with 15.6 g of methyl N-Boc-D-(4-methoxyphenyl)glycinate dissolved in 70 cm3 of anhydrous tetrahydrofuran, and in the presence of 4.48 g of lithium chloride. The portionwise addition of 3.98 g of sodium borohydride is carried out at a temperature in the region of 0° C. After addition of 148 cm3 of absolute ethanol at this same temperature, the temperature is allowed to return to about 20° C. and stirring is continued for 20 hours. After cooling the reaction mass to a temperature in the region of 5° C., 98 cm3 of aqueous 1M sodium hydrogen sulfate solution are added. The mixture is stirred for 3 hours and is then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue is taken up in 220 cm3 of dichloromethane, 70 cm3 of aqueous 1M sodium hydrogen sulfate solution and 30 cm3 of water. The mixture is stirred and then the phases are allowed to separate by settling. The organic phase is separated out and the aqueous phase is extracted with twice 60 cm3 of dichloromethane. The organic extracts are combined and then dried over sodium sulfate, filtered and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. A solid is obtained, which is taken up in 50 cm3 of cyclohexane; the crystals are then spin-filtered and dried in an over under reduced pressure (10 Pa) at a temperature in the region of 60° C. 12.47 g of tert-butyl (1R)-1-(4-methoxyphenyl)-2-hydroxyethylcarbamate are obtained in the form of a white solid melting at 138° C.

1. waitfor 30 minutes at a temperature in the region of 30° C
2. customThe reaction mass is evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C
3. addition61 cm3 of aqueous 5% sodium hydrogen carbonate solution are added to the residue
4. customobtained
5. extractionthe mixture is then extracted with 3 times 100 cm3 of dichloromethane
6. customThe aqueous phase is separated out after settling
7. customis then evaporated as above
8. customThe solid obtained
9. concentrationto ⅔ of its volume by concentration under the above conditions
10. extractionThe mixture is extracted with 3 times 100 cm3 of dichloromethane
11. dry with materialdried over magnesium sulfate
12. filtrationfiltered
13. customevaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C
14. customThe crystals obtained
15. customare dried under reduced pressure (5 kPa) at about 20° C