Sodium Hydroxide → (S)-(4-Fluorophenyl)oxirane

Temperature

21 °C

Dissolve (1S)-2-bromo-1-(4-fluorophenyl)ethanol (1650 g, 7.53 mol) in 6.8 L of methyl tert-butyl ether. Add NaOH (2M, in H2O; 4.93 L) while the mixture is at 20° C. Stir the mixture for 3 h while maintaining it at 20-22° C. Separate the layers and extract the aqueous layer with methyl tert-butyl ether (1×2 L). Combine the organic phases; wash the organic phases with brine (1×2 L); dry over Na2SO4; and filter; concentrate the filtrate to give a residue. Purify via silica gel flash column chromatography using a 50:1 mixture of petroleum ether:EtOAce to elute the product. Concentrate the product fractions to give the title compound as a pale yellow oil (880 g, 84%). 1H NMR (300 MHz, CDCl3): 7.27-7.21 (m, 2H), 7.06-7.01 (m, 2H), 3.86 (dd, J=2.6, 4.0 Hz, 1H), 3.16 (dd, J=4.1, 5.5 Hz, 1H), 2.79 (dd, J=2.6, 5.4 Hz, 1H); ee value: 97.5% (AD-H 250 mm×4.6 mm×5 μm column using 99:5 hexanes:ethyl alcohol at 25° C. with a flow rate of 1.0 mL/min).

1. customis at 20° C
2. customSeparate the layers
3. extractionextract the aqueous layer with methyl tert-butyl ether (1×2 L)
4. washwash the organic phases with brine (1×2 L)
5. dry with materialdry over Na2SO4
6. filtrationand filter
7. concentrationconcentrate the filtrate
8. customto give a residue
9. customPurify via silica gel flash column chromatography
10. additiona 50:1 mixture of petroleum ether
11. washEtOAce to elute the product
12. concentrationConcentrate the product fractions

ORD record

ord-6b6cf18093bc4fc0864de04ebf28c3a4

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08993568B2