反应详情

To an ice cooled solution (0° C.) of (S)-1-(5-fluoro-2-methoxy-phenyl)-ethanol (see H. C. Brown, Tet. Letts., 35 (14), 2141-4, 1994. Optical purity of alcohol: >99.5% e.e. (based on SFC on a chiral column: Chiralpak IA (250*4.6 mm i.d.), eluent 5% methanol alcohol in carbon dioxide, Flow rate 4 mL/min, temp. 40° C., back pressure 150 bar, Rt=2.16 min (opposite enantiomer Rt=2.35 min))) (2.00 g, 11.7 mmol), triphenylphosphine (3.54 g, 13.5 mmol, 1.15 eq.) and 3-hydroxy-2-nitro-pyridine (1.81 g, 12.9 mmol, 1.1 eq) in toluene (100 mL) was added a solution of diisopropyl azodicarboxylate (2.73 g, 13.5 mmol, 1.15 eq.) in toluene (20 mL) at such a rate as to maintain the temperature below 10° C. The resulting mixture was stirred at room temperature for 18 hr. The crude reaction mixture was extracted with aqueous potassium hydroxide solution (2M, 2×50 mL). The organic phase was washed with brine and dried over magnesium sulphate before filtering. The filtrate was evaporated under reduced pressure to give an orange semi solid material. This material was suspended in diethyl ether and heptane (80:20 by volume) and filtered. This filtrate was evaporated under reduced pressure. The residue was purified by chromatography on silica gel eluting with a gradient of diethyl ether in heptane (50:50 to 80:20 by volume) to produce the title compound as a pale yellow oil (3.48 g, 86%).

1. temperatureto maintain the temperature below 10° C
2. customThe crude reaction mixture
3. extractionwas extracted with aqueous potassium hydroxide solution (2M, 2×50 mL)
4. washThe organic phase was washed with brine
5. dry with materialdried over magnesium sulphate
6. filtrationbefore filtering
7. customThe filtrate was evaporated under reduced pressure
8. customto give an orange semi solid material
9. filtrationheptane (80:20 by volume) and filtered
10. customThis filtrate was evaporated under reduced pressure
11. customThe residue was purified by chromatography on silica gel eluting with a gradient of diethyl ether in heptane (50:50 to 80:20 by volume)