Boron trifluoride etherate → 4-Bromo-1-chloro-2-(4-ethoxy-benzyl)-benzene

HRID 1058002Notes

Reaction equation

HRID 1058002 reaction equation
[SiH](CC)(CC)CC.[Br:8][C:9]1[CH:10]=[CH:11][C:12]([Cl:26])=[C:13]([CH:25]=1)[C:14]([C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH3:24])=[CH:18][CH:17]=1)=O.B(F)(F)F.CCOCC>ClCCCl.CC#N>[CH3:24][CH2:23][O:22][C:19]1[CH:18]=[CH:17][C:16]([CH2:14][C:13]2[CH:25]=[C:9]([Br:8])[CH:10]=[CH:11][C:12]=2[Cl:26])=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherate2×HCID 12052Triethylsilane2×HCID 10020105(5-Bromo-2-chlorophenyl)(4-ethoxyphenyl)methanone

Product 1

HCID 99964494-Bromo-1-chloro-2-(4-ethoxy-benzyl)-benzeneYield 61.4%

Reagents, catalysts & solvents 1

HCID 22402149Acetonitrile 1,2-dichloroethaneSolvent

Conditions

Temperature
20 °C

Procedure

To a stirred solution of Et3SiH (400 mL, 2.51 mol and 5-bromo-2-chloro-4′-ethoxybenzophenone (390 g, 1.15 mol) in 900 mL of a 1:2 mixture 1,2-dichloroethane/MeCN at 10° C. was added BF3.Et2O (150 mL, 1.58 mol) at such a rate that the temperature did not exceed 20°. Caution a moderate exotherm insues during the addition. After stirring overnight at 20° C., HPLC revealed the reaction to be 90% complete. After adding an additional 40 mL Et3SiH and 15 mL of BF3.Et2O, the reaction was heated to 50° for 3 hr. (Note elevated temperatures increase formation of the Ritter reaction product N-acetyl 5-bromo-2-chloro-4′-ethoxydiphenylmethylamine). Upon cooling, the reaction was quenched with 120 g of KOH in 300 mL of H2O. After stirring 2 hr, the layers were separated. The aqueous layer was extracted 2× with CH2Cl2; the combined organic layers were washed 1× with 300 mL portions of 2M KOH, 2× with H2O containing 10% brine to aid phase separation and with brine 2× prior to drying over Na2SO4. After removal of the volatiles, the residue was recrystallized from absolute EtOH to yield 230 g of 5-bromo-2-chloro-4′-ethoxydiphenylmethane as a white solid.

Workup

  1. customdid not exceed 20°
  2. additionCaution a moderate exotherm insues during the addition
  3. customthe reaction
  4. temperaturethe reaction was heated to 50° for 3 hr
  5. temperatureincrease
  6. temperatureUpon cooling
  7. customthe reaction was quenched with 120 g of KOH in 300 mL of H2O
  8. stirringAfter stirring 2 hr
  9. customthe layers were separated
  10. extractionThe aqueous layer was extracted 2× with CH2Cl2
  11. washthe combined organic layers were washed 1× with 300 mL portions of 2M KOH, 2× with H2O containing 10% brine
  12. customphase separation
  13. dry with materialwith brine 2× prior to drying over Na2SO4
  14. customAfter removal of the volatiles
  15. customthe residue was recrystallized from absolute EtOH

Sources & evidence

ORD record
ord-210086fe3a454d228668c4a63bb03646
Source dataset
uspto-grants-2003_02
Patent number
US06515117B2

Reaction notes

Loading…