Ammonium Chloride → Ethyl 4-[3-(trifluoromethoxy)benzyl]benzoate

HRID 2359324Notes

Reaction equation

HRID 2359324 reaction equation
[Cl-].[Li+].Br[CH2:4][C:5]1[CH:15]=[CH:14][C:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:7][CH:6]=1.[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:20]=[C:21](Br)[CH:22]=[CH:23][CH:24]=1.CC(C1C=CC=C(C(C)C)C=1N1[C-]=[N+](C2C(C(C)C)=CC=CC=2C(C)C)CC1)C.[Cl-].[NH4+]>[Zn].CC(C1C=CC=C(C(C)C)C=1N1[CH-]N(C2C(C(C)C)=CC=CC=2C(C)C)CC1)C.C1C=NC=C(Cl)C=1.Cl[Pd]Cl.BrCCBr.C[Si](Cl)(C)C.C1COCC1>[F:16][C:17]([F:26])([F:27])[O:18][C:19]1[CH:24]=[C:23]([CH:22]=[CH:21][CH:20]=1)[CH2:4][C:5]1[CH:15]=[CH:14][C:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:7][CH:6]=1

Participants

11

Reactant 5

HCID 25517Ammonium ChlorideHCID 433294Lithium ChlorideHCID 5199641-Bromo-3-(trifluoromethoxy)benzeneHCID 954261Ethyl 4-(bromomethyl)benzoateHCID 10883669SIPr

Product 1

HCID 58046326Ethyl 4-[3-(trifluoromethoxy)benzyl]benzoateYield 101.7%

Reagents, catalysts & solvents 5

HCID 6397ChlorotrimethylsilaneCatalystHCID 78391,2-DibromoethaneCatalystHCID 23994ZincCatalyst2×HCID 588388791,3-Bis[2,6-di(propan-2-yl)phenyl]imidazolidin-2-ide;3-chloropyridine;dichloropalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of zinc (807 mg, 12.3 mmol) and lithium chloride (523 mg, 12.3 mmol) under argon was warmed for 10 minutes using a hot air gun, allowed to cool and then anhydrous THF (50 mL) added. The zinc was activated by treatment with 1,2-dibromoethane (39 mg, 0.21 mmol) and TMSCl (4.3 mg, 0.04 mmol). To the resulting mixture at 25° C. was added ethyl 4-(bromomethyl)benzoate (1.0 g, 4.15 mmol) and the mixture stirred for 15 minutes. 3-(Trifluoromethoxy)bromobenzene (694 mg, 2.88 mmol) was added, followed by (1,3-bis(2,6-diisopropylphenyl)imidazolidene)(3-chloropyridyl)palladium(II) dichloride [PEPPSI™-SIPr] (28 mg, 0.04 mmol) and the mixture stirred at 25° C. for 1 hour. Saturated ammonium chloride solution was added and the crude product extracted with ether. The ether extract was washed with brine, dried over Na2SO4 and the solvent evaporated in vacuo. The crude product was purified by silica gel column chromatography eluting with 7:3 hexane:ethyl acetate to afford the title compound (950 mg, 71%).

Workup

  1. temperaturewas warmed for 10 minutes
  2. temperatureto cool
  3. stirringthe mixture stirred at 25° C. for 1 hour
  4. extractionthe crude product extracted with ether
  5. extractionThe ether extract
  6. washwas washed with brine
  7. dry with materialdried over Na2SO4
  8. customthe solvent evaporated in vacuo
  9. customThe crude product was purified by silica gel column chromatography
  10. washeluting with 7:3 hexane

Sources & evidence

ORD record
ord-42f1bf1861394012932bf6d5969b32ba
Source dataset
uspto-grants-2014_04
Patent number
US08685977B2

Reaction notes

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