2-Chloroaniline → 5-Bromo-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid

HRID 494684Notes

Reaction equation

HRID 494684 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[NH2:18].[Br:19][C:20]1[C:21]([F:31])=[C:22]([F:30])[C:23](F)=[C:24]([CH:28]=1)[C:25]([OH:27])=[O:26]>C1COCC1>[Br:19][C:20]1[C:21]([F:31])=[C:22]([F:30])[C:23]([NH:18][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[Cl:11])=[C:24]([CH:28]=1)[C:25]([OH:27])=[O:26]

Participants

5

Reactant 3

HCID 72402-ChloroanilineHCID 2733832Lithium HexamethyldisilazideHCID 111186375-Bromo-2,3,4-trifluorobenzoic acid

Product 1

HCID 218669915-Bromo-2-(2-chlorophenylamino)-3,4-difluorobenzoic acidYield 66.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of LiHMDS (49.0 mL, 2 M in THF/heptane) in THF (40 mL) was added 2-chlorophenylamine (6.50 mL, 60.6 mmol) at −78° C. After vigorous stirring for 10 minutes, a solution of 5-bromo-2,3,4-trifluoro-benzoic acid (2) (7.70 g, 30.2 mmol) in THF (60 mL) was added. The dry-ice bath was removed and the reaction mixture stirred for 4 hours at room temperature. The mixture was concentrated, treated with 10% aqueous HCl (75 mL), and extracted with EtOAc. The combined organic extracts were dried over MgSO4, filtered, and concentrated. Purification by trituration with boiling CH2Cl2 gave 7.24 g (66%) of the desired acid (3) as a yellow solid

Workup

  1. customThe dry-ice bath was removed
  2. stirringthe reaction mixture stirred for 4 hours at room temperature
  3. concentrationThe mixture was concentrated
  4. additiontreated with 10% aqueous HCl (75 mL)
  5. extractionextracted with EtOAc
  6. dry with materialThe combined organic extracts were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by trituration with boiling CH2Cl2

Sources & evidence

ORD record
ord-d35fb952c63e4d738d1ca0bf9a1c78c9
Source dataset
uspto-grants-2009_05
Patent number
US07538120B2

Reaction notes

Loading…