反応 #42668

反応方程式

sodium bicarbonate

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

2,3-difluorophenylboronic acid

water

→

title compound

収率 87.4%

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

収率 87.4%

溶媒

DCM NaHCO3

dioxane

反応条件

後処理

1. 1
   温度then heated to 35° C
2. 2
   workup.WAITAfter 4 h
3. 3
   その他the layers separated
4. 4
   乾燥The combined organics were dried over magnesium sulfate
5. 5
   ろ過filtered
6. 6
   濃縮concentrated
7. 7
   その他to give a residue that
8. 8
   その他was purified by silica gel chromatography (5%→60% ethyl acetate/hexanes)

実験手順

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).

出典