Dimethylformamide → 7-Bromo-5-fluoro-3,4-dihydronaphthalen-1(2H)-one

HRID 2089481Notes

Reaction equation

HRID 2089481 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11]([OH:13])=O)=[C:4]([F:14])[CH:3]=1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[Cl-].[Al+3].[Cl-].[Cl-]>ClCCl>[Br:1][C:2]1[CH:7]=[C:6]2[C:5]([CH2:8][CH2:9][CH2:10][C:11]2=[O:13])=[C:4]([F:14])[CH:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 606766074-(4-Bromo-2-fluorophenyl)butanoic acid

Product 1

HCID 591994027-Bromo-5-fluoro-3,4-dihydronaphthalen-1(2H)-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 4-(4-bromo-2-fluoro-phenyl)-butyric acid (0.625 g, 2.154 mmol) and DMF (0.0084 g, 0.108 mmol) in dichloromethane (10 mL) is added oxalyl chloride (0.558 g, 4.309 mmol). The mixture is stirred for 30 min and concentrated in vacuo at room temperature to give a yellow oil, which is re-dissolved in dichloromethane (20 mL) and added dropwise to aluminum chloride (0.402 g, 3.016 mmol) in dichloromethane (20 mL). The mixture is refluxed for 3.5 hours, and then poured into ice-water. The resulting mixture is extracted twice with diethyl ether. The organic phases are combined, washed with saturated aqueous NaHCO3, dried over MgSO4, filtered through a cotton plug, and concentrated. The resulting residue is purified by silica gel flash chromatography (hexanes-ethyl acetate, 19:1 to 9:1) to afford 7-bromo-5-fluoro-3,4-dihydro-2H-naphthalen-1-one; 1H NMR (400 MHz, CDCl3) δ ppm 2.13-2.19 (m, 2 H), 2.67 (t, J=6.6 Hz, 2 H), 2.90 (t, J=6.2 Hz, 2 H), 7.40 (dd, J=8.5, 1.9 Hz, 1 H), 7.98 (s, 1 H).

Workup

  1. concentrationconcentrated in vacuo at room temperature
  2. customto give a yellow oil, which
  3. temperatureThe mixture is refluxed for 3.5 hours
  4. extractionThe resulting mixture is extracted twice with diethyl ether
  5. washwashed with saturated aqueous NaHCO3
  6. dry with materialdried over MgSO4
  7. filtrationfiltered through a cotton plug
  8. concentrationconcentrated
  9. customThe resulting residue is purified by silica gel flash chromatography (hexanes-ethyl acetate, 19:1 to 9:1)

Sources & evidence

ORD record
ord-29d6d011e2b4463489dec32bada90f10
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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