Water → [tert-Butoxycarbonyl-(2-phenylamino-propyl)-amino]-acetic acid

A mixture of [tert-Butoxycarbonyl-(2-oxo-propyl)-amino]-acetic acid (1 eq), aniline (1.2 eq) and Ti(OiPr)4(1.25 eq) was stirred at RT for 30 min under N2 flow. The mixture was diluted with dry EtOH (0.8 M) and NaBH3(CN) (0.67 eq) was added. The reaction mixture was stirred for 24 h, after which water was added and the resulting white, inorganic precipitate was filtered, and washed with EtOH. The filtrate was concentrated under reduced pressure and the resulting crude was diluted with EtOAc. The solution was extracted with 1N NaOH and the aqueous phase was washed with EtOAc twice. The aqueous phase was acidified to pH 1 by addition of conc. HCl at 0° C. and washed with EtOAc. The pH of the collected aqueous phase was adjusted to pH 3-4 and product extracted with EtOAc (5×). The collected organic phases were dried (Na2SO4), filtered and evaporated to provide LL1 as a transparent oil. MS (ES) C16H24N2O4 requires: 308 found: 309 (M+H)+.

1. additionwas added
2. stirringThe reaction mixture was stirred for 24 h
3. filtrationthe resulting white, inorganic precipitate was filtered
4. washwashed with EtOH
5. concentrationThe filtrate was concentrated under reduced pressure
6. additionthe resulting crude was diluted with EtOAc
7. extractionThe solution was extracted with 1N NaOH
8. washthe aqueous phase was washed with EtOAc twice
9. additionThe aqueous phase was acidified to pH 1 by addition of conc. HCl at 0° C.
10. washwashed with EtOAc
11. extractionextracted with EtOAc (5×)
12. dry with materialThe collected organic phases were dried (Na2SO4)
13. filtrationfiltered
14. customevaporated
15. customto provide LL1 as a transparent oil

ORD-Eintrag

ord-d4af2d05a6ba4e2eb66b56d0a3b058f4

Quelldatensatz

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08268827B2