Carbon Dioxide → 5-Bromo-3-dibenzylamino-2-fluorobenzoic acid

HRID 1436716Notes

Reaction equation

HRID 1436716 reaction equation
[CH2:1]([N:8]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:9]1[CH:14]=[C:13]([Br:15])[CH:12]=[CH:11][C:10]=1[F:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.C(NC(C)C)(C)C.[C:44](=[O:46])=[O:45]>C1COCC1>[Br:15][C:13]1[CH:14]=[C:9]([N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:10]([F:16])=[C:11]([CH:12]=1)[C:44]([OH:46])=[O:45]

Participants

7

Reactant 5

HCID 280Carbon DioxideHCID 7912DiisopropylamineHCID 2724682Lithium diisopropylamideHCID 67207617N,N-dibenzyl-5-bromo-2-fluoroanilineHCID 178418339Butyllithium

Product 1

HCID 688175625-Bromo-3-dibenzylamino-2-fluorobenzoic acidYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Add dropwise a solution of dibenzyl-(5-bromo-2-fluorophenyl)-amine (4.00 g, 10.8 mmol) in THF (12 mL) to a solution of lithium diisopropylamide, freshly prepared by adding n-butyllithium (1.6 M in hexanes, 7.09 mL, 11.3 mmol) to diisopropylamine (1.74 mL, 12.4 mmol) in THF (25 mL) at −78° C. Stir the resulting yellow solution at −78 C. for 45 min. Pour into a dry ice slurry containing about 100 g in dry THF (40 mL). Stir the solution until it reaches room temperature. Concentrate the solution and dissolve the residue in 10% aqueous potassium hydroxide solution (40 mL) and extract with diethyl ether (70 mL). Acidify the aqueous layer to about pH=3 with concentrated HCl. Extract the aqueous layer with diethyl ether (2×200 mL). Combine the organic layers and wash with water (150 mL), dry (magnesium sulfate) and concentrate to give the title compound as a solid (1.81 g, 40%).

Workup

  1. customfreshly prepared
  2. stirringStir the solution until it
  3. customreaches room temperature
  4. concentrationConcentrate the solution
  5. dissolutiondissolve the residue in 10% aqueous potassium hydroxide solution (40 mL)
  6. extractionextract with diethyl ether (70 mL)
  7. extractionExtract the aqueous layer with diethyl ether (2×200 mL)
  8. washCombine the organic layers and wash with water (150 mL)
  9. dry with materialdry (magnesium sulfate)
  10. concentrationconcentrate

Sources & evidence

ORD record
ord-537272072c044c258f5220f1293fd274
Source dataset
uspto-grants-2009_11
Patent number
US07618978B2

Reaction notes

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