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

HRID 1190856Notes

Reaction equation

HRID 1190856 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>[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

7

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 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Under a stream of nitrogen, 5.0 g (29.07 mmol) of 4-bromo-2-picoline and 10.2 g (60.95 mmol) of ethyl 4-fluorobenzoate are placed in a round-bottomed flask and dissolved in 50 mL of anhydrous tetrahydrofuran. The mixture 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 room temperature for 2 hours, cooled to 5° C., and 100 mL of water are then gradually added. The medium is then diluted with 250 mL of ethyl acetate and 100 mL of water. The organic phase is separated out and the aqueous phase is extracted twice with 100 mL of ethyl acetate. The organic phases are then combined, dried over sodium sulfate and filtered. 15 g of silica are then added to the filtrate, and the resulting mixture is stirred and then concentrated under reduced pressure. The powder obtained is used as a solid deposit for a chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (9/1). 7.5 g (88%) of compound are obtained in the form of a yellow powder.

Workup

  1. additionAfter addition
  2. temperaturecooled to 5° C.
  3. customThe organic phase is separated out
  4. extractionthe aqueous phase is extracted twice with 100 mL of ethyl acetate
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. addition15 g of silica are then added to the filtrate
  8. stirringthe resulting mixture is stirred
  9. concentrationconcentrated under reduced pressure
  10. customThe powder obtained
  11. washeluting with a mixture of cyclohexane and ethyl acetate (9/1)

Sources & evidence

ORD record
ord-30eb634c17db46aaa2f06460821d3c3c
Source dataset
uspto-grants-2014_03
Patent number
US08680096B2

Reaction notes

Loading…