Sodium hydride → 3-(5-Bromo-2-fluoro-phenyl)-1-o-tolyl-propan-1-one

HRID 59768Notes

Reaction equation

HRID 59768 reaction equation
[H-].[Na+].[O:3]=[C:4]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH3:16])[CH2:5][C:6](OC)=O.[Br:17][C:18]1[CH:23]=[CH:22][C:21]([F:24])=[C:20](CBr)[CH:19]=1>O1CCCC1>[Br:17][C:18]1[CH:19]=[CH:20][C:21]([F:24])=[C:22]([CH2:6][CH2:5][C:4]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH3:16])=[O:3])[CH:23]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2760278Methyl 3-(2-methylphenyl)-3-oxopropanoateHCID 135532954-Bromo-2-(bromomethyl)-1-fluorobenzene

Product 1

HCID 712929733-(5-Bromo-2-fluoro-phenyl)-1-o-tolyl-propan-1-oneYield 67.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% in oil, 2.1 g, 52 mmol) and methyl 3-oxo-3-o-tolylpropanoate (10 g, 52 mmol) were suspended in tetrahydrofuran and 4-bromo-2-(bromomethyl)-1-fluoro-benzene (15.3 g, 57 mmol) was added. After complete conversion, the mixture was quenched with ice and a saturated solution of ammonium chloride and extracted with n-heptane. The combined organic layers were washed once with a saturated solution of ammonium chloride, water and brine. The organic layer was dried over magnesium sulfate and evaporated to dryness. The obtained yellow oil was dissolved in 25 ml of acetic acid, 25 ml of concentrated hydrochloric acid and 20 ml of 1,4-dioxane and heated under reflux for 4 h until LC/MS showed consumption of the starting material. 50 ml of water and 100 ml of tert-butyl methyl ether were added and the product was extracted. The combined organic layers were washed once with saturated solution of ammonium chloride, water and brine. The organic layer was dried over magnesium sulfate and evaporated to dryness. The residue was purified by column chromatography (silica gel, heptane/ethyl acetate gradient) to give 11.2 g of 3-(5-bromo-2-fluoro-phenyl)-1-o-tolyl-propan-1-one as a colorless oil.

Workup

  1. customAfter complete conversion, the mixture was quenched with ice
  2. extractiona saturated solution of ammonium chloride and extracted with n-heptane
  3. washThe combined organic layers were washed once with a saturated solution of ammonium chloride, water and brine
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. customevaporated to dryness
  6. dissolutionThe obtained yellow oil was dissolved in 25 ml of acetic acid
  7. temperature25 ml of concentrated hydrochloric acid and 20 ml of 1,4-dioxane and heated
  8. temperatureunder reflux for 4 h until LC/MS
  9. customconsumption of the starting material
  10. addition50 ml of water and 100 ml of tert-butyl methyl ether were added
  11. extractionthe product was extracted
  12. washThe combined organic layers were washed once with saturated solution of ammonium chloride, water and brine
  13. dry with materialThe organic layer was dried over magnesium sulfate
  14. customevaporated to dryness
  15. customThe residue was purified by column chromatography (silica gel, heptane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-d48c9b82c3244b939420779b9463ce7a
Source dataset
uspto-grants-2016_09
Patent number
US09440941B2

Reaction notes

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