Ammonia → HCID 46184655, compound

Temperature

-78 °C

To a solution of 4-bromobenzaldehyde (80 μL 0.48 mmol) in tetrahydrofuran (THF) (0.8 mL) at −78° C. in a dry ice/acetone bath) was added n-butyl lithium (nBuLi) (0.38 mL, 1.6 M in hexanes) dropwise. The solution was stirred for ten minutes at −78° C. Next, copper cyanide (22 mg, 0.24 mmol) was added and the reaction mixture was warmed to −30° C. briefly until the solids dissolved. After cooling to −78° C., (R)-1-((R)-oxiran-2-yl)-octan-1-ol (27.6 mg, 0.16 mmol) was added dropwise. The reaction mixture was stirred at −20° C. overnight at which time TLC indicated completion of the reaction. Aqueous 10% NH3 in saturated NH4Cl was added to the reaction, which was subsequently allowed to warm to room temperature and extracted with ether. The collected organic layers were washed with brine, dried with MgSO4, filtered, and concentrated. Flash chromatography using a gradient from 0 to 25% EtOAc/Hexanes gave the title compound (39.5 mg, 0.12 mmol, 75%). 1H NMR (CDCl3, 400 MHz) δ: 7.40 (2H, d, J=8 Hz), 7.25 (2H, d, J=8.8 Hz), 5.37 (1H, s), 3.70-3.66 (1H, m), 3.51-3.47 (1H, m), 3.34 (6H, s), 2.90 (1H, dd, J=0.01, 13.4 Hz), 2.76 (1H, dd, J=0.02, 13.6 Hz), 2.02 (1H, d, J=5.6 Hz), 1.90 (1H, d, J=4.4 Hz), 1.51-1.29 (12H, m), 0.88 (3H, t, J=6.4 Hz); LRMS (APCI+) calcd for C18H29O3 [M-MeOH]: 293.2; found 293.5.

1. temperaturethe reaction mixture was warmed to −30° C. briefly until the solids
2. dissolutiondissolved
3. temperatureAfter cooling to −78° C.
4. stirringThe reaction mixture was stirred at −20° C. overnight at which time TLC
5. customcompletion of the reaction
6. temperatureto warm to room temperature
7. extractionextracted with ether
8. washThe collected organic layers were washed with brine
9. dry with materialdried with MgSO4
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-272b30b7b4e34bf59f460664cf823acc

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08859615B2