Tetrahydrofuran → HCID 67404601, compound

Temperature

-78 °C

In a 250 mL round bottom flask, 3.2054 g (10.2330 mmol, 1.0 eq) of the protected alcohol was dissolved in 83 mL of reagent-grade THF under N2 atmosphere. The solution was then cooled to −78° C. using a dry ice/acetone bath. 4.50 mL (11.2563 mmol, 1.1 eq) of the n-BuLi (2.5 M in hexanes) was added dropwise to the solution. The reaction was allowed to stir for 30 min while maintaining lowered temperature. 3.54 mL (15.3495 mmol, 1.5 eq) of the triisopropyl borate was added to the reaction slowly at −78° C. Upon complete addition of the triisopropyl borate, the reaction was allowed to gradually warm to room temperature overnight, maintaining inert atmosphere. The following morning, the reaction was quenched by the slow addition of 20 mL of 6M HCl (aq). The reaction was allowed to stir for 1 h. The reaction solution was then diluted with 50 mL of EtOAc and poured into 50 mL of H2O. The layers were separated, and the aqueous layer was extracted with EtOAc (2×50 mL). The organic layers were combined, washed with brine, and dried over Na2SO4. The solution was decanted and the solvent was removed under reduced pressure. The oily material was then taken up in 25 mL of DCM and stirred together with 25 mL of 10% NaOH solution. The layers were separated and the aqueous layer was neutralized with 2N HCl. The aqueous layer was then re-extracted with EtOAc (3×30 mL) and the organic layer was washed with brine (1×50 mL) and dried over Na2SO4. The solvent was then removed under reduced pressure, yielding a colorless oil. LCMS (m/e): 177 (M+H); 1H NMR (400 MHz, acetone-d6) δ ppm 1.22-1.28 (m, 3H) 3.82-3.92 (m, 1H) 4.14 (dd, J=10.84, 3.95 Hz, 1H) 7.15-7.31 (m, 2H) 7.35-7.48 (m, 1H) 7.75 (d, J=7.17 Hz, 1H).

1. temperaturewhile maintaining
2. temperatureto gradually warm to room temperature overnight
3. temperaturemaintaining inert atmosphere
4. customThe following morning, the reaction was quenched by the slow addition of 20 mL of 6M HCl (aq)
5. stirringto stir for 1 h
6. additionThe reaction solution was then diluted with 50 mL of EtOAc
7. additionpoured into 50 mL of H2O
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with EtOAc (2×50 mL)
10. washwashed with brine
11. dry with materialdried over Na2SO4
12. customThe solution was decanted
13. customthe solvent was removed under reduced pressure
14. stirringstirred together with 25 mL of 10% NaOH solution
15. customThe layers were separated
16. extractionThe aqueous layer was then re-extracted with EtOAc (3×30 mL)
17. washthe organic layer was washed with brine (1×50 mL)
18. dry with materialdried over Na2SO4
19. customThe solvent was then removed under reduced pressure
20. customyielding a colorless oil

ORD record

ord-1565a3711dcb400b96d5615c19402ebe

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08623911B2