Pyridine → (+)-(S,R)-6-Fluoro-3,4-dihydro-2-(2-oxiranyl)-2H-1-benzopyran

Temperature

1 °C

(R)-1-((S)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethane-1,2-diol (0.27 g, 1.27 mmol) was dissolved in dichloromethane (10 ml) under nitrogen atmosphere and pyridine (510 μl) added under stirring. The reaction mixture was then cooled to 1° C. and tosyl chloride (0.24 g, 1.27 mmol) in dichloromethane (3 ml) was added over a period of 2.5 h. The reaction was quenched with saturated ammonium chloride (1 ml) and further diluted with dichloromethane (10 ml) and demi water (10 ml). The aqueous layer was separated and further extracted with dichloromethane (15 ml). The collected organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo to furnish a colourless oil. Said oil was dissolved in methanol (3 ml) and dichloromethane (6 ml) under stirring in nitrogen atmosphere and potassium carbonate (0.32 g, 2.35 mmol) added. The reaction mixture was left to stir for 15 h at 25° C. The reaction was then diluted with water (10 ml) and dichloromethane (10 ml). The separated aqueous layer was further extracted with dichloromethane (20 ml). The collected organic layers were dried over magnesium sulfate and concentrated in vacuo to furnish crude (S)-6-fluoro-3,4-dihydro-2-((R)-oxiran-2-yl)-2H-chromene as a yellow oil. Separation via chomatography on silica, using heptane:ethyl acetate 9:1 as eluent, furnished 30 mg of (S)-6-fluoro-3,4-dihydro-2-((R)-oxiran-2-yl)-2H-chromene as a colourless oil (12% yield).

1. customThe reaction was quenched with saturated ammonium chloride (1 ml)
2. additionfurther diluted with dichloromethane (10 ml) and demi water (10 ml)
3. customThe aqueous layer was separated
4. extractionfurther extracted with dichloromethane (15 ml)
5. dry with materialThe collected organic layers were dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto furnish a colourless oil
9. additionadded
10. waitThe reaction mixture was left
11. stirringto stir for 15 h at 25° C
12. extractionThe separated aqueous layer was further extracted with dichloromethane (20 ml)
13. dry with materialThe collected organic layers were dried over magnesium sulfate
14. concentrationconcentrated in vacuo
15. customto furnish crude (S)-6-fluoro-3,4-dihydro-2-((R)-oxiran-2-yl)-2H-chromene as a yellow oil
16. customSeparation via chomatography on silica

ORD record

ord-ddfa9d5d57a84cc5a0f6da0257a0b133

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07999124B2