O-benzyl-N-((tert-butoxy)carbonyl)-L-tyrosine → Benzyl L-leucinate

The pH of the aqueous layer obtained by the washing procedure with 5% aqueous sodium carbonate solution and saturated brine one more time was 9.6, and the content of Boc-Tyr(Bn)-OBt in the obtained organic layer was 0.2% and the content of Boc-Tyr(Bn) was 0.1%. Subsequently, the obtained organic layer was washed once with saturated brine (15 ml) and then washed by adding 5% aqueous potassium hydrogen sulfate solution (5 ml) and saturated brine (15 ml) thereto. Then, saturated brine (15 ml), water (15 ml) and chlorobenzene (8 ml) were added to the organic layer, and the resulting mixture was condensed under reduced pressure, thereby distilling off chlorobenzene until the total amount of the solution was 7.29 g. As a result, a solid was deposited. When chlorobenzene (10 ml) and water (15 ml) were added thereto, and the resulting mixture was allowed to mature at room temperature for 1 hour, a homogenous slurry was formed. Then, after the slurry was allowed to mature by stirring for 1 hour under ice-cooling, the deposited solid was filtered, and sequentially washed with chlorobenzene (2 ml) and water (2 ml), and then dried under vacuum, thereby a white solid was obtained. The purity of the target Boc-Tyr(Bn)-Gly-Gly-Phe-Leu-OBn (SEQ ID NO: 4) was 92%, and the content of Tyr(Bn) was 2.1%. Further, the crystallization yield was 93%, and the acquisition yield relative to the Leu-OBn.TsOH salt was 64%.

1. washSubsequently, the obtained organic layer was washed once with saturated brine (15 ml)
2. washwashed
3. additionby adding 5% aqueous potassium hydrogen sulfate solution (5 ml) and saturated brine (15 ml)
4. additionThen, saturated brine (15 ml), water (15 ml) and chlorobenzene (8 ml) were added to the organic layer
5. customcondensed under reduced pressure
6. distillationdistilling off chlorobenzene until the total amount of the solution
7. additionWhen chlorobenzene (10 ml) and water (15 ml) were added
8. customa homogenous slurry was formed
9. temperaturecooling
10. filtrationthe deposited solid was filtered
11. washsequentially washed with chlorobenzene (2 ml) and water (2 ml)
12. customdried under vacuum
13. customa white solid was obtained
14. customFurther, the crystallization yield was 93%

ORD record

ord-1928dabd4a854918937a523533991bf2

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346850B2