Ethylacetate heptane → 3-Fluoro-2-(3-hydroxypropyl)-6-methoxyphenol

To a solution of 4.46 g of 6-fluoro-2-hydroxy-3-methoxybenzaldehyde in 50 ml of dichloromethane there was added 10 g of (triphenyl phosphoranilidene)acetic acid ethyl ester while cooling on ice. After stirring at room temperature for 30 minutes, the reaction mixture was poured into a silica gel column and elution was performed with heptane-ethyl acetate=3:1. The eluate was concentrated under reduced pressure. The residue was dissolved in 100 ml of ethyl acetate, 1 g of 10% palladium-carbon was added, and the mixture was stirred at room temperature for 7 hours under a hydrogen atmosphere. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was dissolved in 100 ml of THF, and then 2 g of lithium borohydride was added while cooling on ice and the mixture was stirred overnight at room temperature. After adding 1N hydrochloric acid to the reaction mixture while cooling on ice, extraction was performed with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The desiccating agent was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate-heptane) to give the title compound (4.78 g) as a solid.

1. temperaturewhile cooling on ice
2. additionthe reaction mixture was poured into a silica gel column and elution
3. concentrationThe eluate was concentrated under reduced pressure
4. dissolutionThe residue was dissolved in 100 ml of ethyl acetate
5. addition1 g of 10% palladium-carbon was added
6. stirringthe mixture was stirred at room temperature for 7 hours under a hydrogen atmosphere
7. filtrationThe reaction mixture was filtered through celite
8. concentrationthe filtrate was concentrated under reduced pressure
9. dissolutionThe residue was dissolved in 100 ml of THF
10. addition2 g of lithium borohydride was added
11. temperaturewhile cooling on ice
12. stirringthe mixture was stirred overnight at room temperature
13. additionAfter adding 1N hydrochloric acid to the reaction mixture
14. temperaturewhile cooling on ice, extraction
15. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
16. filtrationThe desiccating agent was filtered off
17. concentrationthe filtrate was concentrated under reduced pressure
18. customThe residue was purified by silica gel column chromatography (ethyl acetate-heptane)

ORD record

ord-ea89998bd47f4f3f8148f106a775b577

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07816522B2