tert-Butyl hydroperoxide → (2s-trans)-[3-(3,4-Dichloro-phenyl)-oxiranyl]-methanol

Temperature

-20 °C

To a suspension of powdered 4 Å molecular sieves (3.2 g) in DCM (144 mL) was added Ti(O-iPr)4 (0.864 mL, 2.93 mmol), (+)-L-diisopropyl tartrate (0.924 mL, 4.39 mmol), and t-BuOOH (5.5 M in decane, 10.8 mL, 59.4 mmol). The mixture was cooled to −20° C. stirred for 1 h. A solution of 3,4-dichlorocinnamyl alcohol (6.0 g, 29.5 mmol) in DCM (30 mL) was added via cannula. After 18 h at −20° C., the reaction was quenched by addition of 10% aq. NaOH and brine (10%, 4 mL). The cooling bath was removed, and after stirring for 20 min, Et2O (30 mL) was added followed by MgSO4 (8 g) and diatomaceous earth (8 g). The mixture was stirred rapidly for 15 min then was filtered through a pad of diatomaceous earth, washing with excess Et2O. The filtrate was concentrated, and the desired epoxide was crystallized from the yellow residue with a warm DCM/hexanes mixture to afford 4.22 g (65%) of pale yellow crystals. The epoxide was determined to be >95% ee by 1H NMR analysis of both the R- and S-Mosher ester derivatives. 1H NMR (400 MHz, CDCl3): 7.42 (d, J=8.3, 1H), 7.37 (d, J=2.0, 1H), 7.13 (dd, J=8.3, 2.0, 1H), 4.04 (dd, J=12.9, 2.2, 1H), 3.91 (d, J=2.0, 1H), 3.82 (dd, J=12.9, 3.4, 1H), 3.18-3.11 (m, 1H), 1.80 (br s, 1H).

1. waitAfter 18 h at −20° C.
2. customthe reaction was quenched by addition of 10% aq. NaOH and brine (10%, 4 mL)
3. customThe cooling bath was removed
4. stirringafter stirring for 20 min
5. additionEt2O (30 mL) was added
6. stirringThe mixture was stirred rapidly for 15 min
7. filtrationthen was filtered through a pad of diatomaceous earth
8. washwashing with excess Et2O
9. concentrationThe filtrate was concentrated
10. customthe desired epoxide was crystallized from the yellow residue with a warm DCM/hexanes mixture

ORD record

ord-ef7bdb6247134a7d828a84c54c6a5644

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07855292B2