4-(Trifluoromethyl)aniline → 2-Azido-4-bromo-N-(4-trifluoromethylphenyl)-benzamide

HRID 270681Notes

Reaction equation

HRID 270681 reaction equation
[N:1]([C:4]1[CH:12]=[C:11]([Br:13])[CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=O)=[N+:2]=[N-:3].[NH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1>O=S(Cl)Cl.CN(C)C1C=CN=CC=1.C(Cl)Cl>[N:1]([C:4]1[CH:12]=[C:11]([Br:13])[CH:10]=[CH:9][C:5]=1[C:6]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:22])([F:23])[F:24])=[CH:17][CH:16]=1)=[O:8])=[N+:2]=[N-:3]

Participants

6

Reactant 2

HCID 99644-(Trifluoromethyl)anilineHCID 860515482-Azido-4-bromobenzoic acid

Product 1

HCID 860515492-Azido-4-bromo-N-(4-trifluoromethylphenyl)-benzamideYield 84%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent

Procedure

The product of Step 1 (6.4 g, 0.026 mol) was heated in SOCl2 (30 mL) at reflux for 2 h. The excess reagent was then evaporated and chased with toluene (2×10 mL). The residue was dissolved in dry CH2Cl2 (20 mL) and added dropwise to a solution of 4-(dimethylamino)pyridine (3.2 g, 0.026 mol) and 4-aminobenzotrifluoride (4.3 g, 0.026 mol) in CH2Cl2 (40 mL) cooled in ice. When addition was complete (10 min), the mixture was stirred and warmed to room temperature over 1 h, then washed with 2N HCl (15 mL), 2N Na2CO3 solution (15 mL), brine (10 mL), dried (MgSO4) and concentrated to give 8.4 g (84% yield) of product as a buff solid. 1H NMR (360 MHz, CDCl3): 7.40 (1H, d, J 1.4 Hz), 7.44 (1H, dd, J 1.4 and 8.5 Hz), 7.63 (2H, d, J8.5 Hz), 7.80 (2H, d, J 8.5 Hz), 8.14 (1H, d, J 8.5 Hz).

Workup

  1. temperatureat reflux for 2 h
  2. customThe excess reagent was then evaporated
  3. dissolutionThe residue was dissolved in dry CH2Cl2 (20 mL)
  4. temperaturecooled in ice
  5. additionWhen addition
  6. custom(10 min)
  7. washwashed with 2N HCl (15 mL), 2N Na2CO3 solution (15 mL), brine (10 mL)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-879f38a8009946e3ac86e301d99b8020
Source dataset
uspto-grants-2008_11
Patent number
US07449585B2

Reaction notes

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