Ethyl trifluoroacetate → HCID 53650418, compound

HRID 370355Notes

Reaction equation

HRID 370355 reaction equation
[Cl:1][C:2]1[CH:14]=[CH:13][C:5]([NH:6][C:7](=[O:12])[C:8]([CH3:11])([CH3:10])[CH3:9])=[C:4]([F:15])[CH:3]=1.[Li]C(C)(C)C.[F:21][C:22]([F:29])([F:28])[C:23](OCC)=[O:24]>C1COCC1.CCCCC>[CH3:9][C:8]([CH3:11])([CH3:10])[C:7]([NH:6][C:5]1[C:4]([F:15])=[CH:3][C:2]([Cl:1])=[CH:14][C:13]=1[C:23](=[O:24])[C:22]([F:29])([F:28])[F:21])=[O:12]

Participants

6

Reactant 3

HCID 9794Ethyl trifluoroacetateHCID 4070755HCID 4070755, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 53650418HCID 53650418, compoundYield 43.8%

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred, cooled (-50° C.) solution of 0.92 g (4.0 mmol) of 4'-chloro-2'-fluoro-2,2-dimethylpropionanilide in 10 mL of THF was added 2.5 mL (4.2 mmol) of 1.7 M t-BuLi in pentane over 5 min. The solution was stirred for 5 min. and treated with 1.0 mL (8.4 mmol) of ethyl trifluoroacetate over 2 min. The reaction was warmed to ambient temperature, stirred 15 min., and quenched with IN aqueous citric acid. The mixture was extracted with ether, and the organic extract was washed sequentially with water then brine. The solution was dried(MgSO4) and concentrated under reduced pressure to give an oil. The crude amide was chromatographed on silica gel (elution with 3:1 hexanes-ether followed by 1:1 hexanes-ether) to give 570 mg (43%) of 2'-(trimethylacetamido)-5'-chloro-3'-fluoro-2,2,2-trifluoroacetophenone as an off-white solid. 1H NMR(300 MHz, CDCl3) δ 8.68(s, 1H); 7.45-7.47(m, 1H); 7.08(dd, 1H, J=9.5, 2.6 Hz); 1.3(s, 9H). High resolution mass spec: calculated for C13H13NO2ClF4 (M+H)+ : 326.0571, found: 326.0579.

Workup

  1. stirringstirred 15 min.
  2. customquenched with IN aqueous citric acid
  3. extractionThe mixture was extracted with ether
  4. extractionthe organic extract
  5. washwas washed sequentially with water
  6. concentrationconcentrated under reduced pressure
  7. customto give an oil
  8. customThe crude amide was chromatographed on silica gel (elution with 3:1 hexanes-ether followed by 1:1 hexanes-ether)

Sources & evidence

ORD record
ord-914ceec85ef748fba8ff101e2778f47b
Source dataset
uspto-grants-2000_10
Patent number
US06140499

Reaction notes

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