Diisopropylamine → HCID 46872552, compound

Temperature

-78 °C

n-BuLi (2.5 M in hexane, 17.6 mL, 44 mmol) was added to a solution of diisopropylamine (6.65 mL, 47.4 mmol) in THF (48 mL) stirred at −78° C. The solution was stirred at −78° C. for 5 min and warmed to 0° C. for 15 min. Borane-ammonia complex (90%, 1.55 g, 45.2 mmol) was added and the resulting mixture was stirred at 0° C. for 15 min, warmed to room temperature for 15 min and then cooled to 0° C. A solution of amide 26 (6.62 g, 11.3 mmol) in THF (35 mL) was added dropwise and the reaction was stirred at 0° C. for 1 h and then at room temperature for 2 h. The mixture was cooled to 0° C. and quenched carefully with saturated aqueous NH4Cl. The mixture was extracted with Et2O and the combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (step gradient of 4:1 to 7:3 hexane/EtOAc) to afford the alcohol 27 (4.57 g, 96%) as a colorless oil: IR (film) 3410, 1612, 1513, 1249, 1067, 1038 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.26 (d, J=8.6 Hz, 2H), 6.88 (d, J=8.6 Hz, 2H), 4.44 (d, J=11.7 Hz, 1H), 4.39 (d, J=11.7 Hz, 1H), 3.81 (s, 3H), 3.51 (m, 2H), 3.44 (dd, J=5.6, 3.4 Hz, 1H), 3.37 (dd, J=10.6, 6.5 Hz, 1H), 3.22 (dd, J=9.0, 7.0 Hz, 1H), 2.03-1.95 (m, 1H), 1.78-1.62 (m, 2H), 1.53 (br, 1H), 1.41 (ddd, J=13.5, 7.5, 5.8 Hz, 1H), 0.95 (d, J=6.9 Hz, 3H), 0.94 (d, J=6.7 Hz, 3H), 0.88 (s, 9H), 0.87 (d, J=6.9 Hz, 3H), 0.04 (s, 3H), 0.03 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 159.2, 130.9, 129.4, 113.9, 77.5, 72.8, 67.7, 55.4, 38.3, 38.0, 33.6, 33.2, 26.3, 18.6, 18.0, 15.6, 15.5, −3.5, −3.8; [α]20D−6.3 (c 1.7, CHCl3).

1. stirringThe solution was stirred at −78° C. for 5 min
2. temperaturewarmed to 0° C. for 15 min
3. additionBorane-ammonia complex (90%, 1.55 g, 45.2 mmol) was added
4. stirringthe resulting mixture was stirred at 0° C. for 15 min
5. temperaturewarmed to room temperature for 15 min
6. temperaturecooled to 0° C
7. stirringthe reaction was stirred at 0° C. for 1 h
8. temperatureThe mixture was cooled to 0° C.
9. customquenched carefully with saturated aqueous NH4Cl
10. extractionThe mixture was extracted with Et2O
11. washthe combined organic extracts were washed with brine
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customThe residue was purified by flash chromatography (step gradient of 4:1 to 7:3 hexane/EtOAc)

ORD record

ord-53323c1b24584c608f7629083834791f

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07321046B2