Reaction #168752

Reaction equation

acetone

NH4Cl

diisopropyl amine

nBuLi

hexane

4-bromo-1-fluoro benzene

→

title compound

2-(5-Bromo-2-fluoro-phenyl)-propan-2-ol

Solvents

THF

Conditions

Workup

1. 1
   Otherthe temperature below −70° C
2. 2
   workup.STIRRINGAfter stirring for 2 h at −75° C.
3. 3
   workup.STIRRINGthe reaction mixture was stirred for 1 h at −75° C.
4. 4
   Temperaturewarmed up to −50° C.
5. 5
   ExtractionThe mixture was extracted with TBME, organic phases
6. 6
   Washwere washed with aqueous KHSO4 solution, saturated NaHCO3 solution and brine
7. 7
   Dryingdried over MgSO4
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated
10. 10
    OtherThe crude product was crystallized from hexane

Procedure

To a solution of diisopropyl amine (57.3 ml, 402 mmol) in THF (500 ml) was added under argon a 1.6 M solution of nBuLi in hexane (260 ml, 416 mmol) below −50° C. After stirring for 30 min at −75° C., 4-bromo-1-fluoro benzene (31.1 ml, 277 mmol) was added while keeping the temperature below −70° C. After stirring for 2 h at −75° C., acetone (41.2 ml, 554 mmol) was added below −65° C. and the reaction mixture was stirred for 1 h at −75° C., warmed up to −50° C. and poured onto 10% aqueous NH4Cl solution. The mixture was extracted with TBME, organic phases were washed with aqueous KHSO4 solution, saturated NaHCO3 solution and brine, dried over MgSO4, filtered and concentrated. The crude product was crystallized from hexane to provide the title compound as white crystals: TLC (hexane-EtOAc 3:1): Rf=0.45; HPLC RtH5=1.045 min; 1H NMR (360 MHz, CDCl3): δ 7.74 (dd, 1H), 7.36 (m, 1H), 6.93 (dd, 1H), 2.04 (d, 1H), 1.63 (s, 6H).

Source