Reacción #42668

Ecuación de reacción

sodium bicarbonate

benzyl (2R,5E)-2-[bis(tert-butoxycarbonyl)amino]-6-nitrohex-5-enoate

2,3-difluorophenylboronic acid

water

→

title compound

Rendimiento 87.4%

Benzyl (5S)-N,N-bis(tert-butoxycarbonyl)-5-(2,3-difluorophenyl)-6-nitro-D-norleucinate

Rendimiento 87.4%

Disolventes

DCM NaHCO3

dioxane

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathen heated to 35° C
2. 2
   workup.WAITAfter 4 h
3. 3
   Otrothe layers separated
4. 4
   SecadoThe combined organics were dried over magnesium sulfate
5. 5
   Filtraciónfiltered
6. 6
   Concentraciónconcentrated
7. 7
   Otroto give a residue that
8. 8
   Otrowas purified by silica gel chromatography (5%→60% ethyl acetate/hexanes)

Procedimiento

A solution of benzyl (2R,5E)-2-[bis(tert-butoxycarbonyl)amino]-6-nitrohex-5-enoate (34.0 g, 73.2 mmol), 2,3-difluorophenylboronic acid (28.9 g, 183.0 mmol) and water (4.62 mL, 256.2 mmol) in dioxane (240 mL) was degassed with argon for 15 min. To this solution was added sodium bicarbonate (3.08 g, 36.6 mmol), (S)-BINAP (1.28 g, 2.05 mmol) and acetylacetanotobis(ethylene)rhodium(I) (0.472 g, 1.83 mmol). The mixture was stirred at RT for 2 min then heated to 35° C. After 4 h, 255 mg of (S)-BINAP and 94 mg of acetylacetanotobis(ethylene)rhodium(I) were added. After an additional 2 h the reaction was diluted with DCM/NaHCO3, the layers separated and the aqueous phase was backwashed with another portion of DCM. The combined organics were dried over magnesium sulfate, filtered and concentrated to give a residue that was purified by silica gel chromatography (5%→60% ethyl acetate/hexanes) to give the title compound (37.0 g, 87%) contaminated with ˜5% 5R isomer. MS 379.1 (M+1−Boc).

Fuente