Hydrogen Bromide → 1-(4-Fluorophenyl)-2-(4-methylthiophenyl)-2-bromoethanone

HRID 862610Notes

Reaction equation

HRID 862610 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:18])[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([S:16][CH3:17])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.Br.BrBr.[Br:22]C(Br)=O>C(O)(=O)C.ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:18])[CH:9]([C:10]2[CH:15]=[CH:14][C:13]([S:16][CH3:17])=[CH:12][CH:11]=2)[Br:22])=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 260Hydrogen BromideHCID 24408Bromine2×HCID 79057Carbonyl bromideHCID 112539741-(4-Fluorophenyl)-2-(4-methylthiophenyl)ethanone

Product 1

HCID 541605321-(4-Fluorophenyl)-2-(4-methylthiophenyl)-2-bromoethanone

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A 1 L three necked round bottomed flask equipped with reflux condenser, magnetic stir bar, thermometer adapter, and constant pressure addition funnel was charged with the intermediate from Step 2, (55.5 g, 0.21 mol), acetic acid (250 mL) and 33% HBr in acetic acid (120 mL). The solution was stirred and treated with bromine (11.1 mL, 0.21 mol) from the addition funnel at such a rate that the bromine color was discharged rapidly, ca. 15 minutes. After an additional 10 minutes at room temperature, the solution was filtered through a Buchner funnel and the filtrate concentrated in vacuo to give an orange solid. The crude bromoketone was dissolved in dichloromethane and washed with 1N NaHSO3, dried over anhydrous MgSO4, filtered and concentrated in vacuo to give 68.8 g of 1-(4-fluorophenyl)-2-(4-methylthiophenyl)-2-bromoethanone as a yellow solid which was used directly without further purification. The crude bromoketone was dissolved in 300 mL acetone and 150 mL of water and heated to reflux for 2.5 hours. The solution was concentrated in vacuo and the residue taken up in dichloromethane, washed with saturated aqueous sodium bicarbonate, brine, dried over anhydrous magnesium sulfate, filtered and reconcentrated in vacuo to give a light yellow solid that was crystallized from a mixture of dichloromethane and isooctane to provide 37.8 g (65%) of pure 1-(4-fluorophenyl)-2-(4-methylthiophenyl)-2-hydroxy-ethanone: mp 90°-92° C.

Workup

  1. temperaturewith reflux
  2. additioncondenser, magnetic stir bar, thermometer adapter, and constant pressure addition funnel
  3. waitAfter an additional 10 minutes at room temperature
  4. filtrationthe solution was filtered through a Buchner funnel
  5. concentrationthe filtrate concentrated in vacuo
  6. customto give an orange solid
  7. washwashed with 1N NaHSO3
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-742643a492ac48cda2cd4bae9c730f3a
Source dataset
uspto-grants-1998_02
Patent number
US05719163

Reaction notes

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