Reaktion #1857554

Reaktionsgleichung

(Z)-benzyl 3-bromo-2-((tert-butoxycarbonyl)amino)acrylate

K3PO4

1-methoxy-4-((((2S,3S)-6-methyl-3-((S)-1-propoxyallyl)heptan-2-yl)oxy)methyl)benzene

9-BBN

→

title compound

Ausbeute 67.0%

(6S,7S,Z)-benzyl 2-((tert-butoxycarbonyl)amino)-7-((S)-1-((4-methoxybenzyl)oxy)ethyl)-10-methyl-6-propoxyundec-2-enoate

Ausbeute 67.0%

Lösungsmittel

DMF

H2O

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction vessel was fitted with an air condenser
2. 2
   Temperaturslowly warmed to 55° C
3. 3
   workup.WAITThe solution became homogeneous and bright orange after 30 min
4. 4
   TemperaturThe reaction was maintained at this temperature for 20 h, at which point the color
5. 5
   TemperaturThe reaction was cooled to room temperature
6. 6
   Sonstigethe phases were separated
7. 7
   ExtraktionThe aq. phase was extracted with Et2O (3×50 mL)
8. 8
   Waschenthe combined organics were washed with brine (15 mL)
9. 9
   Trocknendried over Na2SO4
10. 10
    Filtrationfiltered
11. 11
    workup.ADDITIONthe filtrate was treated with Celite® (2 scoopula tip-fulls)
12. 12
    SonstigeThe solvent was removed under reduced pressure
13. 13
    Sonstigepurified

Vorschrift

To a solution of 1-methoxy-4-((((2S,3S)-6-methyl-3-((S)-1-propoxyallyl)heptan-2-yl)oxy)methyl)benzene (1.25 g, 3.59 mmol) in THF (3 mL) was added 9-BBN (10.8 mL, 5.38 mmol, 0.5 M in THF) dropwise, and the reaction was stirred at room temperature for 6 h. The reaction mixture was carefully treated with an aq. solution of K3PO4 (3 M, 2.152 mL, 6.46 mmol; gas evolution), followed by a solution of (Z)-benzyl 3-bromo-2-((tert-butoxycarbonyl)amino)acrylate (1.30 g, 3.66 mmol) in DMF (3.59 mL), and PdCl2-dppf (0.262 g, 0.359 mmol). The reaction vessel was fitted with an air condenser and slowly warmed to 55° C. The solution became homogeneous and bright orange after 30 min. The reaction was maintained at this temperature for 20 h, at which point the color had turned a very dark red (almost black). The reaction was cooled to room temperature, diluted with H2O (30 mL), and the phases were separated. The aq. phase was extracted with Et2O (3×50 mL), and the combined organics were washed with brine (15 mL), dried over Na2SO4, filtered, and the filtrate was treated with Celite® (2 scoopula tip-fulls). The solvent was removed under reduced pressure and the resulting adsorbed material was directly loaded onto a column and purified using flash column chromatography (80 g SiO2, 0→25% acetone/hexanes) to afford the title compound (1.50 g, 2.397 mmol, 67%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.40-7.29 (m, 5H), 7.25-7.20 (m, 2H), 6.88-6.80 (m, 2H), 6.59 (app t, J=7.5 Hz, 1H), 6.15 (s, 1H), 5.20 (app d, J=2.2 Hz, 2H), 4.48 (d, J=11.4 Hz, 1H), 4.34 (d, J=11.4 Hz, 1H), 3.78 (s, 3H), 3.57 (p, J=6.2 Hz, 1H), 3.36 (ddd, J=7.3, 5.3, 3.7 Hz, 1H), 3.33-3.19 (m, 2H), 2.36-2.16 (m, 2H), 1.72-1.38 (m, 16H), 1.38-1.13 (m, 6H), 0.91-0.82 (m, 9H); 13C NMR (101 MHz, CDCl3) δ 164.82, 158.99, 153.42, 137.06, 135.73, 131.13, 129.21, 128.52, 128.24, 128.22, 113.70, 80.33, 79.43, 74.78, 71.76, 69.86, 67.00, 55.25, 46.35, 38.73, 30.64, 28.68, 28.19, 25.39, 23.88, 23.47, 22.64, 22.61, 17.08, 10.79; ESIMS m/z 648 ([M+Na]+).

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