Sodium hydride → (R,Z)-2-(hex-3-enyl)oxirane

To a solution of (R,Z)-oct-5-ene-1,2-diol (8.50 g, 58.9 mmol) in THF (230 mL) at 0° C. was added NaH (60% dispersion in mineral oil, 7.06 g, 177 mmol) (7.06 g as dispersion). The mixture was warmed to ambient temperature and stirred for 40 min. The reaction was cooled to 0° C. and triisopropylbenzenesulfonyl chloride (20.7 g, 61.8 mmol) was added. The reaction was warmed to room temp, stirred for 1 h, quenched with H2O and extracted with Et2O. The organics were washed with brine, dried over MgSO4, filtered, and concentrated. Purification by silica gel chromatography (2% Et2O in pentane gradient to 8% Et2O in pentane) gave (R,Z)-2-(hex-3-enyl)oxirane. It was determiined that slight racemization occurred at this step (98% ee to 84% ee). In order to ensure optical purity the enantioenriched product was further resolved using Jacobsen's hydrolytic kinetic resolution (HKR, Step E). 1H NMR (400 MHz, CDCl3): δ 5.41 (1H, m), 5.35 (1H, m), 2.93 (1H, m), 2.75 (1H, dd, J=5.2, 4.4 Hz), 2.49 (1H, dd, J=5.2, 2.8 Hz), 2.20 (2H, q, J=6.8 Hz), 2.06 (2H, quin, 7.6 Hz); 1.59 (2H, m), 0.97 (3H, t, J=7.6 Hz).

1. temperatureThe reaction was cooled to 0° C.
2. temperatureThe reaction was warmed to room temp
3. stirringstirred for 1 h
4. customquenched with H2O
5. extractionextracted with Et2O
6. washThe organics were washed with brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification by silica gel chromatography (2% Et2O in pentane gradient to 8% Et2O in pentane)

ORD record

ord-caf523f482c54e79af7094c5e60aef4e

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07612106B2