1,4-Dibromobenzene → HCID 69152881, compound

HRID 1744166Notes

Reaction equation

HRID 1744166 reaction equation
FC(F)(F)C(O)=O.[CH3:8][C@@H:9]1[CH2:13][NH:12][C@H:11]([C:14]([OH:16])=[O:15])[CH2:10]1.[Br:17][C:18]1[CH:23]=[CH:22][C:21](Br)=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+]>[Cu](I)I.CN(C=O)C>[Br:17][C:18]1[CH:19]=[C:20]([N:12]2[CH2:13][C@@H:9]([CH3:8])[CH2:10][C@H:11]2[C:14]([OH:16])=[O:15])[CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 3

HCID 78041,4-DibromobenzeneHCID 11430Potassium CarbonateHCID 69151595HCID 69151595, compound

Product 1

HCID 69152881HCID 69152881, compound

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

To (4S)-4-methyl-L-proline trifluoroacetate (2.92 g, 8.17 mmol), 1,4-dibromobenzene (2.9 g, 12.27 mmol), potassium carbonate (3.95 g, 28.6 mmol), and copper iodide (315 mg, 1.64 mmol) was added dry DMF (30 mL) under dry nitrogen. The reaction flask was thoroughly degassed with dry nitrogen and heated at 95° C. for 3 days. Water and hexane were added and the organic phase was separated and discarded (to remove excess 1,4-dibromobenzene). The pH of the aqueous phase was adjusted to 3 with aqueous 10% HCl and the product extracted with EtOAc (2×), dried over Na2SO4, concentrated in vacuo and purified by flash chromatography over silica gel (AcOH/EtOAc/Hex, 0.5/49.5/50) to afford (4S)-1-(3-bromophenyl)-4-methyl-L-proline.

Workup

  1. customThe reaction flask was thoroughly degassed with dry nitrogen
  2. additionWater and hexane were added
  3. customthe organic phase was separated
  4. custom(to remove excess 1,4-dibromobenzene)
  5. extractionthe product extracted with EtOAc (2×)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. custompurified by flash chromatography over silica gel (AcOH/EtOAc/Hex, 0.5/49.5/50)

Sources & evidence

ORD record
ord-1ca789fa7b8f4e63949bba1bea94d327
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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