Water → 2-(4-Bromopyridin-2-yl)-1-(4-chlorophenyl)ethanone

HRID 1918194Notes

Reaction equation

HRID 1918194 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].O>O1CCCC1>[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

6

Reactant 4

HCID 962WaterHCID 81785Ethyl 4-chlorobenzoateHCID 27628354-Bromo-2-methylpyridineHCID 57426343Lithium bis(trimethylsilyl)amide

Product 1

HCID 672466412-(4-Bromopyridin-2-yl)-1-(4-chlorophenyl)ethanoneYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

1.0 g (5.8 mmol) of 4-bromo-2-methylpyridine and 2.14 g (11.6 mmol) of ethyl 4-chlorobenzoate are placed under a stream of argon in a round-bottomed flask and dissolved in 10 ml of anhydrous tetrahydrofuran. The solution is cooled to 0° C. and 12 ml of a lithium hexamethyldisilazane (LiHMDS) solution (1M in tetrahydrofuran) are added. After addition, the mixture is heated at 45° C. for 3 h and cooled to ambient temperature, and then water is added. The tetrahydrofuran is subsequently evaporated under reduced pressure and the aqueous phase is extracted three times with ether. The organic phase is separated, dried and concentrated under reduced pressure. The residue obtained is purified by chromatography on silica gel, elution being carried out with a mixture of dichloromethane and heptane. 1.11 g (62%) of compound are obtained.

Workup

  1. additionAfter addition
  2. temperaturethe mixture is heated at 45° C. for 3 h
  3. temperaturecooled to ambient temperature
  4. customThe tetrahydrofuran is subsequently evaporated under reduced pressure
  5. extractionthe aqueous phase is extracted three times with ether
  6. customThe organic phase is separated
  7. customdried
  8. concentrationconcentrated under reduced pressure
  9. customThe residue obtained
  10. customis purified by chromatography on silica gel, elution
  11. additionbeing carried out with a mixture of dichloromethane and heptane

Sources & evidence

ORD record
ord-f76a6fc69c094e18a7c0caee1e8a33be
Source dataset
uspto-grants-2013_12
Patent number
US08618301B2

Reaction notes

Loading…