Sodium hydride → HCID 54400578, compound

Temperature

5 °C

To a stirred solution of (4-bromo-2-fluorophenyl)methanol (10 g, 49.02 mmol) in THF (250 mL) at 0° C., was added 60% NaH (2.93 g, 73.53 mmol) slowly in portions. After addition, the suspension was heated to 5° C. for 30 min, cooled to RT, then was added 1-bromo-2-methoxy ethane (5 mL, 53.92 mmol) and the mixture was stirred at RT for 20 h until complete consumption of (4-bromo-2-fluorophenyl)methanol, as evidenced by TLC analysis. The reaction mixture was diluted with ice cold water (100 mL) and concentrated under reduced pressure. The obtained aqueous residue was extracted with EtOAc (2×150 mL); the combined EtOAc layers were washed with brine solution (50 mL), dried over anhydrous NaSO4, filtered and concentrated. The obtained crude compound was purified by CC using 5% EtOAc in PE as eluent to afford 4-bromo-2-fluoro-1-((2-methoxyethoxy)methyl)benzene (6 g, 47%) as yellow liquid (TLC solvent system: 30% EtOAc-PE; Rf: 0.4).

1. additionAfter addition
2. temperaturecooled to RT
3. concentrationconcentrated under reduced pressure
4. extractionThe obtained aqueous residue was extracted with EtOAc (2×150 mL)
5. washthe combined EtOAc layers were washed with brine solution (50 mL)
6. dry with materialdried over anhydrous NaSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe obtained crude compound
10. customwas purified by CC

ORD record

ord-a2d0288ead224c1aa156ae207fe40b95

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946204B2