Hydrochloric Acid → 3-Fluoro-4′-propyl[1,1′-biphenyl]-4-ol

Temperature

-74 °C

In a nitrogen atmosphere, 44.32 g of 3-fluoro-1-(4-propylphenyl)benzene was dissolved in 220 mL of THF, the resultant solution was cooled to −74° C., and 210 mL of secondary butyl lithium (1.0 mol/L, hexane solution) was added at such a rate that the inside temperature did not exceed −60° C. After stirring at −74° C. for 1 hour, 23.64 g of trimethoxyborane was added at such a rate that the inside temperature did not exceed −60° C. After stirring at −74° C. for 1 hour, the inside temperature was increased to room temperature, and 10% hydrochloric acid was added until the system became acidic. Then, an organic layer was separated, and an aqueous layer was subjected to extraction with toluene. The toluene extract was combined with the organic layer and cooled with ice, and 54 g of a 15% aqueous hydrogen peroxide solution was added to the mixture, followed by stirring under ice cooling for 3 hours. Further, an organic layer was separated, and an aqueous layer was subjected to extraction with toluene. The toluene extract was combined with the organic layer and washed with a 10% aqueous sodium sulfite solution and saturated brine. The organic layer mixture was dried by adding sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was recrystallized from hexane to yield 41.01 g of 2-fluoro-4-(4-propylphenyl)phenol.

1. customdid not exceed −60° C
2. customdid not exceed −60° C
3. stirringAfter stirring at −74° C. for 1 hour
4. temperaturethe inside temperature was increased to room temperature
5. customThen, an organic layer was separated
6. extractionan aqueous layer was subjected to extraction with toluene
7. extractionThe toluene extract
8. temperaturecooled with ice, and 54 g of a 15% aqueous hydrogen peroxide solution
9. additionwas added to the mixture
10. stirringby stirring under ice cooling for 3 hours
11. customFurther, an organic layer was separated
12. extractionan aqueous layer was subjected to extraction with toluene
13. extractionThe toluene extract
14. washwashed with a 10% aqueous sodium sulfite solution and saturated brine
15. customThe organic layer mixture was dried
16. additionby adding sodium sulfate
17. distillationthe solvent was distilled off under reduced pressure
18. customThe residue was recrystallized from hexane

ORD record

ord-8448425102e74cb78ffd46728b4a3b4c

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08916718B2