Trimethylsilyldiazomethane → Ethyl (S)-2-(Boc-amino)-6-diazo-5-oxohexanoate

HRID 2272843Notes

Reaction equation

[Li]CCCC.[Si]([CH:10]=[N+:11]=[N-:12])(C)(C)C.[O:13]=[C:14]1[N:18]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C@H:17]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:16][CH2:15]1>C1COCC1>[C:22]([O:21][C:19]([NH:18][C@@H:17]([CH2:16][CH2:15][C:14](=[O:13])[CH:10]=[N+:11]=[N-:12])[C:26]([O:28][CH2:29][CH3:30])=[O:27])=[O:20])([CH3:23])([CH3:25])[CH3:24]

Participants

Conditions

Temperature: -78 °C

Procedure

n-BuLi (600 mL, 1.5 mol) was added dropwise to a solution of TMSCHN2 (690 mL, 1.38 mol) in dry THF (3 L) at −78° C., and the mixture was stirred at −78° C. for 30 minutes. The mixture was then transferred to a solution of (S)-1-tert-butyl 2-ethyl 5-oxopyrrolidine-1,2-dicarboxylate (300 g, 1.17 mol) in dry THF (3 L) via cannula, and the mixture was stirred at −78° C. for 30 minutes. The reaction mixture was then quenched with sat. NH4Cl solution, and extracted with DCM (3×). The combined organic layer was concentrated under reduced pressure and the crude product was purified by silica gel column chromatography (3:1 petroleum ether:EtOAc) to afford (S)-ethyl 2-((tert-butoxycarbonyl)amino)-6-diazo-5-oxohexanoate (262 g, 75%) as a yellow solid.

Workup

stirringthe mixture was stirred at −78° C. for 30 minutes
customThe reaction mixture was then quenched with sat. NH4Cl solution
extractionextracted with DCM (3×)
concentrationThe combined organic layer was concentrated under reduced pressure
customthe crude product was purified by silica gel column chromatography (3:1 petroleum ether:EtOAc)

Sources & evidence

ORD record: ord-96f6345a24524fcaaf50ef790027c849
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09120795B2

Reaction notes

Loading…