4-Methylmorpholine → Phenylmethyl (3S)-3-[[(1,1-dimethylethoxy)carbonyl]amino]-4-hydroxybutanoate

Temperatur

-5 °C

N-(tert-Butoxycarbonyl)-L-aspartic acid 4-benzyl ester (30 g) was dissolved in dimethoxyethane (90 mL) and the solution was cooled to −5° C. N-Methylmorpholine (10.32 mL) was added followed by a slow addition of isobutyl chloroformate (12.66 mL) such that the reaction temperature was kept below −10° C. The mixture was aged for 0.5 hour. The solids were quickly filtered and washed with dimethoxyethane (90 mL). The filtrate was cooled to −50° C. and a solution of sodium borohydride (4.4 g) in water (45 mL) was added slowly such that the reaction temperature was maintained between −30° C. and −15° C. Water (500 mL) was then added such that the reaction mixture temperature was maintained below −15° C. The suspension was filtered, the solid washed with water (400 μL) and dried to yield benzyl (3S)-3-[(tert-butoxycarbonyl)amino]-4-hydroxybutanoate.

1. customwas kept below −10° C
2. filtrationThe solids were quickly filtered
3. washwashed with dimethoxyethane (90 mL)
4. temperatureThe filtrate was cooled to −50° C.
5. additiona solution of sodium borohydride (4.4 g) in water (45 mL) was added slowly such that the reaction temperature
6. temperaturewas maintained between −30° C. and −15° C
7. additionWater (500 mL) was then added such that the reaction mixture temperature
8. temperaturewas maintained below −15° C
9. filtrationThe suspension was filtered
10. washthe solid washed with water (400 μL)
11. customdried

ORD-Eintrag

ord-a9739360c39a496f931652fe8fc1109d

Quelldatensatz

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07973037B2