Reaction #1272682

ord-cef6c2f5a7714aacae18cc7d23470724

Reaction equation

CC(C)(C)OC(=O)CC[C@H](NC(=O)OCc1ccccc1)C(=O)O
(S)-2-Benzyloxycarbonylamino-pentanedioic acid 5-tert-butyl ester
O=C(OC1CCC1)N1CCNCC1
piperazine-1-carboxylic acid cyclobutyl ester
CCN1CCOCC1
N-ethylmorpholine
CCOC(=O)C(C#N)=NOC(N(C)C)=[N+](C)C.F[B-](F)(F)F
TOTU
→
CC(C)(C)OC(=O)CC[C@H](NC(=O)OCc1ccccc1)C(=O)N1CCN(C(=O)OC2CCC2)CC1
crude product
CC(C)(C)OC(=O)CC[C@H](NC(=O)OCc1ccccc1)C(=O)N1CCN(C(=O)OC2CCC2)CC1
4-((S)-2-Benzyloxycarbonylamino-4-tert-butoxycarbonyl-butyryl)-piperazine-1-carboxylic acid cyclobutyl ester

Reactants

CC(C)(C)OC(=O)CC[C@H](NC(=O)OCc1ccccc1)C(=O)O
(S)-2-Benzyloxycarbonylamino-pentanedioic acid 5-tert-butyl ester
O=C(OC1CCC1)N1CCNCC1
piperazine-1-carboxylic acid cyclobutyl ester
CCN1CCOCC1
N-ethylmorpholine
CCOC(=O)C(C#N)=NOC(N(C)C)=[N+](C)C.F[B-](F)(F)F
TOTU

Reagents

None

Solvents

CCOC(C)=O
ethyl acetate
CN(C)C=O
DMF

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Washsubsequently washed with aqueous LiCl (4%) and saturated aqueous NaHCO3

Procedure

To a solution of 6.0 g (S)-2-Benzyloxycarbonylamino-pentanedioic acid 5-tert-butyl ester in 50 ml DMF were added 3.3 g piperazine-1-carboxylic acid cyclobutyl ester, 9.1 ml N-ethylmorpholine and 5.9 g TOTU. After stirring for 12 h the solution was diluted with ethyl acetate and subsequently washed with aqueous LiCl (4%) and saturated aqueous NaHCO3. The crude product obtained after evaporation of the solvent was used without further purification. Yield: 11.1 g.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08669266B2uspto-grants-2014_03