Tetrahydrofuran → 1-Fluoro-5-methoxynaphthalene

Temperature

2.5 °C

A stirred mixture of 6.8 g of 5-amino-1-methoxynaphthalene, 57 ml THF and 74 ml of 48-50% HBF4 was cooled in an ice/salt bath. To the stirred suspension was added dropwise a solution of 3.00 g of sodium nitrite in 6 ml of water. The mixture was stirred at 0-5° C. for 30 minutes after which 300 ml of ether was added. The mixture was stirred at 0-5° C. for 45 minutes after which it was filtered and the residue washed three times with dry ether. The resulting dark red solid was air dried overnight to yield 12.2 g. The material was dissolved in 70 ml of 1-ethyl-3-methylimidazolium tetrafluoroborate and heated at 70-80° C. for 2 h (gas evolution was observed). The mixture was allowed to cool to room temperature, extracted twice with ether, washed with brine, dried (magnesium sulphate), filtered and concentrated to an oil. The material was dissolved in dichloromethane and flash chromatographed on silica gel, eluting with ethyl acetate/heptane to provide 2.08 g (30%) of 5-fluoro-1-methoxynaphthalene.

1. temperaturewas cooled in an ice/salt bath
2. additionwas added
3. filtrationwas filtered
4. washthe residue washed three times with dry ether
5. customdried overnight
6. customto yield 12.2 g
7. temperatureheated at 70-80° C. for 2 h (gas evolution was observed)
8. temperatureto cool to room temperature
9. extractionextracted twice with ether
10. washwashed with brine
11. dry with materialdried (magnesium sulphate)
12. filtrationfiltered
13. concentrationconcentrated to an oil
14. dissolutionThe material was dissolved in dichloromethane
15. customflash chromatographed on silica gel
16. washeluting with ethyl acetate/heptane

ORD record

ord-7eaaa9a87031421a871ccb534db18be6

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07919628B2