Boron trifluoride → (2R)-1-(5-fluoro-2-methylphenyl)propan-2-ol

An oven dried 3-necked round bottom flask (rbf), which contained a magnetic stirring bar, was sealed with rubber septum having a thermometer. While cooling to rt, the flask was evacuated and backfilled with argon. This sequence was repeated 3 times. In the flask, a solution of 4-fluoro-2-iodo-1-methylbenzene (25 g, 105.9 mmol) in anhydrous THF (800 mL) was stirred at −78° C. in a dry ice/acetone bath under argon gas. After 30 min, 1.4 M sec-BuLi in hexane (83.2 mL, 116.5 mmol) was added dropwise at that temperature for 20 min. After adding, the mixture was stirred at −78° C. in the dry ice/acetone bath for 30 min, and stirred more for 30 min without the bath. And then, the solution was cooled again in the dry ice/acetone to −78° C. and a solution of R-(+)-propylene (8 g, 137.7 mmol) in 50 mL anhydrous THF was added dropwise at the temperature for 10 min. And then, the mixture was cooled to −105° C. and 46.5% solution of BF3 in diethyletherate (19.6 mL) was added dropwise. And the mixture was stirred at −78° C. for 2 h, and then quenched slowly by sat. NH4Cl at −78° C. and stirred at ambient temperature for overnight. Water (20 mL) was added and extracted with EtOAc, dried over anhydrous MgSO4, evaporated and purified by column chromatography (DCM/hexane 9/1) to give (R)-1-(5-fluoro-2-methylphenyl)propan-2-ol (F-1) as pale yellowish oil.

1. customAn oven dried 3-necked round bottom flask (rbf), which
2. customwas sealed with rubber septum
3. customthe flask was evacuated
4. additionAfter adding
5. temperatureAnd then, the mixture was cooled to −105° C.
6. stirringAnd the mixture was stirred at −78° C. for 2 h
7. customquenched slowly by sat. NH4Cl at −78° C.
8. stirringstirred at ambient temperature for overnight
9. additionWater (20 mL) was added
10. extractionextracted with EtOAc
11. dry with materialdried over anhydrous MgSO4
12. customevaporated
13. custompurified by column chromatography (DCM/hexane 9/1)

ORD record

ord-b4281acd532d4fd591e04d9019d1249f

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273055B2