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

HRID 1036641

Reaction equation

HRID 1036641 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.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]([Cl:9])=[CH:11][CH:12]=2)=[O:15])[CH:3]=1

Participants

8

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 4

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

Conditions

Temperature
5 °C

Procedure

5 g (29.07 mmol) of 4-bromo-2-methylpyridine and 11.27 g (61.04 mmol) of ethyl 4-chlorobenzoate 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 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 ambient temperature for 2 h and cooled to 5° C., and then 100 ml of water are gradually added. 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 and the mixture is concentrated 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. 8.4 g (93%) 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
  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. concentrationthe mixture is concentrated under reduced pressure
  9. customThe powder obtained

Sources & evidence

ORD record
ord-0cc6fd4c55374beb86551e6afe289506
Source dataset
uspto-grants-2013_10
Patent number
US08546424B2

Linked notes

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