Benzoic acid, 4-fluoro-, ethyl ester → 2-(4-Bromopyridin-2-yl)-1-(4-fluorophenyl)ethanone

HRID 1036642Notes

Reaction equation

HRID 1036642 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[CH:3]=1.[F:9][C:10]1[CH:20]=[CH:19][C:13]([C:14](OCC)=[O:15])=[CH:12][CH:11]=1.C[Si](C)(C)N[Si](C)(C)C.[Li]>O1CCCC1.C(OCC)(=O)C.O.C1CCCCC1>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][C:14]([C:13]2[CH:19]=[CH:20][C:10]([F:9])=[CH:11][CH:12]=2)=[O:15])[CH:3]=1

Participants

8

Reactant 3

HCID 67976Benzoic acid, 4-fluoro-, ethyl esterHCID 27628354-Bromo-2-methylpyridineHCID 57426343Lithium bis(trimethylsilyl)amide

Product 1

HCID 672466172-(4-Bromopyridin-2-yl)-1-(4-fluorophenyl)ethanoneYield 88%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8078CyclohexaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

5.0 g (29.07 mmol) of 4-bromo-2-picoline and 10.2 g (60.95 mmol) of ethyl 4-fluoro-benzoate are placed under a stream of nitrogen in a round-bottomed flask and dissolved in 50 ml of anhydrous tetrahydrofuran. The solution is cooled to 0° C. and 70 ml (70 mmol) of a lithium hexamethyldisilazane solution (1M in tetrahydrofuran) are added dropwise. After addition, the mixture is stirred at ambient temperature for 2 h before being cooled to 5° C. and gradually adding 100 ml of water to the medium. The medium is subsequently diluted with 250 ml of ethyl acetate and 100 ml of water. The organic phase is separated and the aqueous phase is extracted twice with 100 ml of ethyl acetate. The organic phases are subsequently combined, dried over sodium sulphate and filtered. 15 g of silica are subsequently added to the filtrate before concentrating it under reduced pressure. The powder obtained is used as solid deposit for chromatography on silica gel with a mixture of cyclohexane and ethyl acetate (9/1) as eluent. 7.5 g (88%) of compound are obtained in the form of a yellow powder.

Workup

  1. additionAfter addition
  2. temperaturebefore being cooled to 5° C.
  3. customThe organic phase is separated
  4. extractionthe aqueous phase is extracted twice with 100 ml of ethyl acetate
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. addition15 g of silica are subsequently added to the filtrate
  8. concentrationbefore concentrating it under reduced pressure
  9. customThe powder obtained

Sources & evidence

ORD record
ord-c0a56ba4ce51407fb6c4264abfd39e00
Source dataset
uspto-grants-2013_10
Patent number
US08546424B2

Reaction notes

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