Toluene → Methyl N-{[isopropyl(pent-4-en-1-yl)amino]carbonyl}-3-methyl-L-valinate

To a solution (60 nM) of L-tert-leucine methyl-ester hydrochloride and NaHCO3 (8 eq) in dry THF, a solution 20% w/w of phosgene in toluene (5 eq) was added dropwise at 0° C. and the reaction mixture was stirred at that temperature for 30 minutes. Then the solid was filtered-off and the filtrate evaporated at reduced pressure. The resulting crude yellow oil was taken-up in dry THF (0.3 M) and added dropwise to a stirred solution (0.2 M) of N-isopropylpent-4-en-1-amine and TEA (1 eq). The reaction mixture was stirred at room temperature overnight. Then the mixture was taken-up in EtOAc and washed twice with water and brine. The organic phase was dried over Na2SO4 and the volatiles evaporated at reduced pressure. The crude was purified by flash chromatography eluting with petroleum ether (8) EtOAc (2) using Nynhydrin as stain. Methyl N-{[isopropyl(pent-4-en-1-yl)amino]carbonyl}-3-methyl-L-valinate was obtained as light yellow oil (43%).

1. customthe filtrate evaporated at reduced pressure
2. stirringThe reaction mixture was stirred at room temperature overnight
3. washwashed twice with water and brine
4. dry with materialThe organic phase was dried over Na2SO4
5. customthe volatiles evaporated at reduced pressure
6. customThe crude was purified by flash chromatography
7. washeluting with petroleum ether (8) EtOAc (2)

ORD-Eintrag

ord-e7292bffcf374dfe91155e0d3cc2db5c

Quelldatensatz

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08216999B2