Hydrochloric Acid → 1,2-Difluoro-3-hexyloxyphenol

1,2-Difluoro-3-hexyloxybenzene (s-1) (17.8 g) and THF (500 ml) were placed in a reaction vessel under an atmosphere of nitrogen, and cooled to −74° C. n-Butyllithium (1.57M; n-hexane and cyclohexane solution; 58.0 ml) was added dropwise in the temperature range of −74° C. to −70° C., and the stirring was continued for another 2 hours. Trimethyl borate (9.5 g) in a THF (50 ml) solution was added dropwise in the temperature range of −74° C. to −65° C., and the stirring was continued for 8 hours while the mixture was allowed to return to 25° C. The reaction mixture was poured into a vessel containing 1N-hydrochloric acid (100 ml) and ice-water (500 ml) and mixed with them. Ethyl acetate (300 ml) was added, and mixture was then allowed to stand until it had separated into organic and aqueous layers, and the extraction was carried out. The resulting organic layers were separated, and washed successively with water, a saturated aqueous solution of sodium hydrogencarbonate and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue and acetic acid (100 ml) were placed in a reaction vessel at room temperature under an atmosphere of nitrogen, and an aqueous solution of hydrogen peroxide (31%; 10.1 ml) was added dropwise in the temperature range of 25° C. to 30° C., and the stirring was continued for another 2 hours. The reaction mixture was poured into a vessel containing an aqueous solution of sodium hydrogen sulfite (100 ml) and ethyl acetate (300 ml) and mixed with them. The mixture was then allowed to stand until it had separated into organic and aqueous layers, and the extraction was carried out. The resulting organic layers were separated, and washed successively with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to give 1,2-difluoro-3-hexyloxyphenol (s-20) (12.8 g). The yield based on the compound (s-1) was 66.6%.

1. additionwas added dropwise in the temperature range of −74° C. to −70° C.
2. waitthe stirring was continued for 8 hours while the mixture
3. customto return to 25° C
4. additionThe reaction mixture was poured into a vessel
5. additionmixed with them
6. customhad separated into organic and aqueous layers
7. extractionthe extraction
8. customThe resulting organic layers were separated
9. washwashed successively with water
10. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and brine, and then dried over anhydrous magnesium sulfate
11. distillationThe solvent was distilled off under reduced pressure
12. customThe residue and acetic acid (100 ml) were placed in a reaction vessel at room temperature under an atmosphere of nitrogen
13. additionan aqueous solution of hydrogen peroxide (31%; 10.1 ml) was added dropwise in the temperature range of 25° C. to 30° C.
14. waitthe stirring was continued for another 2 hours
15. additionThe reaction mixture was poured into a vessel
16. additioncontaining an aqueous solution of sodium hydrogen sulfite (100 ml) and ethyl acetate (300 ml)
17. additionmixed with them
18. customhad separated into organic and aqueous layers
19. extractionthe extraction
20. customThe resulting organic layers were separated
21. washwashed successively with water and brine
22. dry with materialdried over anhydrous magnesium sulfate
23. distillationThe solvent was distilled off under reduced pressure

ORD record

ord-bfb714c6281f4fecb0e0525cfdaf0f57

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580147B2