Acetonitrile → 1-Chloro-2-(4-ethoxybenzyl)-4-iodobenzene

HRID 913347Notes

Reaction equation

HRID 913347 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH3:19])=[CH:13][CH:12]=1)=O.C(#N)C.C([SiH](CC)CC)C.C(=O)(O)[O-].[Na+]>C(OC)(C)(C)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][C:3]=1[CH2:9][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH3:19])=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 12052TriethylsilaneHCID 516892Sodium BicarbonateHCID 57432783(2-Chloro-5-iodophenyl)(4-ethoxyphenyl)methanone

Product 1

HCID 252075821-Chloro-2-(4-ethoxybenzyl)-4-iodobenzene

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
5 °C

Procedure

A jacketed 1 L three-necked round bottom flask with mechanical stirrer, rubber septum with temperature probe and gas bubbler was charged with crude (2-chloro-5-iodophenyl)(4-ethoxyphenyl)methanone (30.13 g, 77.93 mmol), acetonitrile (300 mL, KF=0.004 wt % water) and the suspension was set stirring under nitrogen and was cooled to about 5° C. Then triethylsilane (28 mL, 175.30 mmol, 2.25 equiv) was added followed by boron trifluoride-diethyletherate (24 mL, 194.46 mmol, 2.50 equiv) which was added over about 30 seconds. The reaction was warmed to ambient over 30 min and was stirred for 17 hours. The reaction was diluted with methyl tert-butyl ether (150 mL) followed by saturated aq sodium bicarbonate (150 mL) which was added over about 1 minutes. Mild gas evolution was noticed and the biphasic solution was stirred at ambient for 45 minutes. The upper organic phase was washed with saturated aq. sodium bicarbonate (100 mL), and with saturated aq. sodium chloride (50 mL). The washed extract was concentrated on a rotary evaporator to about one half of its original volume and was diluted with water (70 mL). Further concentration in vacuo at 45° C. was done until white prills formed which were allowed to cool to ambient while stirring. After about 30 minutes at ambient, the suspended solids were isolated by filtration, washed with water (30 mL), and were dried in vacuo at 45° C. After about 2.5 hours, this afforded 1-chloro-2-(4-ethoxybenzyl)-4-iodobenzene as a slightly waxy white granular powder (28.28 g, 98.2 area % by HPLC at 220 nm, 97.4% “as-is” yield).

Workup

  1. additionwas added over about 30 seconds
  2. temperatureThe reaction was warmed
  3. stirringwas stirred for 17 hours
  4. additionwas added over about 1 minutes
  5. stirringthe biphasic solution was stirred at ambient for 45 minutes
  6. washThe upper organic phase was washed with saturated aq. sodium bicarbonate (100 mL)
  7. extractionThe washed extract
  8. concentrationwas concentrated on a rotary evaporator to about one half of its original volume
  9. additionwas diluted with water (70 mL)
  10. concentrationFurther concentration in vacuo at 45° C.
  11. customformed which
  12. temperatureto cool to ambient
  13. stirringwhile stirring
  14. customAfter about 30 minutes at ambient, the suspended solids were isolated by filtration
  15. washwashed with water (30 mL)
  16. customwere dried in vacuo at 45° C
  17. waitAfter about 2.5 hours

Sources & evidence

ORD record
ord-b302658f9e1b48e797ac3792a0202d90
Source dataset
uspto-grants-2011_09
Patent number
US08026347B2

Reaction notes

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