Tetrahydrofuran → tert-Butyl 2-[(tert-butoxycarbonyl)amino]-2-(3,5-difluorophenyl)propanoate

Reaktionsgleichung

[CH3:1][C:2]([CH3:5])([O-:4])[CH3:3].[K+].C(OC([N:14]([CH:22]([C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([F:31])[CH:25]=1)[CH3:23])[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=O)(C)(C)C.C1C[O:35][CH2:34]C1>>[C:18]([O:17][C:15]([NH:14][C:22]([C:24]1[CH:25]=[C:26]([F:31])[CH:27]=[C:28]([F:30])[CH:29]=1)([CH3:23])[C:34]([O:4][C:2]([CH3:5])([CH3:3])[CH3:1])=[O:35])=[O:16])([CH3:19])([CH3:20])[CH3:21]

Komponenten

Edukt 3

HCID 8028Tetrahydrofuran2×

HCID 23665647Potassium tert-butoxide

HCID 66864402Di-tert-butyl [1-(3,5-difluorophenyl)ethyl]imidodicarbonate

Produkt 1

HCID 66865158tert-Butyl 2-[(tert-butoxycarbonyl)amino]-2-(3,5-difluorophenyl)propanoate

Versuchsvorschrift

To a stirred suspension of potassium tert-butoxide (64 g, 570 mmol) in THF (800 mL) at −78° C. was added a solution of di-tert-butyl[1-(3,5-difluorophenyl)ethyl]imidodicarbonate (68 g, 190 mmol) in THF (480 mL), dropwise, over 45 min. The reaction mixture was allowed to warm to ambient temperature and stirring was continued for 1 h. The reaction mixture was cooled to −78° C. and quenched with 1 N aqueous HCl (600 mL), warmed to 0° C., and poured into Et2O (750 mL). The organic layer was extracted and the aqueous layer was extracted further with Et2O (750 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with hexane:EtOAc—100:0 to 80:20, to give the title compound. MS: m/z=295 (M+1).