Ethyl 4-chlorobenzoate → 2-(4-Bromopyridin-2-yl)-1-(4-chlorophenyl)ethanone

HRID 1190855

Reaction equation

HRID 1190855 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[CH:3]=1.[Cl: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]([Cl:9])=[CH:11][CH:12]=2)=[O:15])[CH:3]=1

Participants

7

Reactant 3

HCID 81785Ethyl 4-chlorobenzoateHCID 27628354-Bromo-2-methylpyridineHCID 57426343Lithium bis(trimethylsilyl)amide

Product 1

HCID 672466412-(4-Bromopyridin-2-yl)-1-(4-chlorophenyl)ethanoneYield 93%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

Under a stream of nitrogen, 5 g (29.07 mmol) of 4-bromo-2-methylpyridine and 11.27 g (61.04 mmol) of ethyl 4-chlorobenzoate are placed in a round-bottomed flask and dissolved in 50 mL of anhydrous tetrahydrofuran. The solution is cooled to 5° 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, which is then concentrated under reduced pressure. The powder obtained is used as solid deposit for a chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (9/1). 8.4 g (93%) of compound are obtained in the faun 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, which
  8. concentrationis then concentrated under reduced pressure
  9. customThe powder obtained
  10. washeluting with a mixture of cyclohexane and ethyl acetate (9/1)

Sources & evidence

ORD record
ord-40d0f7c59b3d436b984409578b2de185
Source dataset
uspto-grants-2014_03
Patent number
US08680096B2

Linked notes

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