Ethyl trifluoroacetate → 1-(4-Chloro-2-fluorophenyl)-2,2,2-trifluoroethan-1-one

HRID 1911206Notes

Reaction equation

HRID 1911206 reaction equation
[Li]CCCC.[Cl:6][C:7]1[CH:12]=[CH:11][C:10](I)=[C:9]([F:14])[CH:8]=1.[F:15][C:16]([F:23])([F:22])[C:17](OCC)=[O:18]>C1COCC1>[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([C:17](=[O:18])[C:16]([F:23])([F:22])[F:15])=[C:9]([F:14])[CH:8]=1

Participants

5

Reactant 3

HCID 9794Ethyl trifluoroacetateHCID 27365624-Chloro-2-fluoro-1-iodobenzeneHCID 178418339Butyllithium

Product 1

HCID 247268361-(4-Chloro-2-fluorophenyl)-2,2,2-trifluoroethan-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of n-BuLi (1.6 M in hexanes, 4.68 mmol, 2.93 mL) in dry THF was slowly added 4-chloro-2-fluoro-1-iodo-benzene 67h (3.9 mmol, 1.0 g) at −78° C. under N2. The mixture was stirred for 1 h at −78° C. and ethyl trifluoroacetate 67b (0.51 mL, 4.29 mmol) was added. The reaction was allowed to warm to room temperature overnight and was quenched with saturated aqueous NH4Cl solution. The mixture was extracted with EtOAc. The organic extracts were concentrated and purified by flash column chromatography (silica gel, 15% EtOAc/hexanes) to give compound 67i.

Workup

  1. customat −78° C.
  2. temperatureto warm to room temperature overnight
  3. customwas quenched with saturated aqueous NH4Cl solution
  4. extractionThe mixture was extracted with EtOAc
  5. concentrationThe organic extracts were concentrated
  6. custompurified by flash column chromatography (silica gel, 15% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f568ad404ce94d209eaa5cfaefa1fd16
Source dataset
uspto-grants-2013_12
Patent number
US08604017B2

Reaction notes

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