Potassium Phosphate, Tribasic → HCID 131734627, compound

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]+).

1. customThe reaction vessel was fitted with an air condenser
2. temperatureslowly warmed to 55° C
3. waitThe solution became homogeneous and bright orange after 30 min
4. temperatureThe reaction was maintained at this temperature for 20 h, at which point the color
5. temperatureThe reaction was cooled to room temperature
6. customthe phases were separated
7. extractionThe aq. phase was extracted with Et2O (3×50 mL)
8. washthe combined organics were washed with brine (15 mL)
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. additionthe filtrate was treated with Celite® (2 scoopula tip-fulls)
12. customThe solvent was removed under reduced pressure
13. custompurified

ORD record

ord-365c6e6762f44375b460bf35e614a8d6

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09247741B2