1-Bromo-2-(bromomethyl)-4-(trifluoromethyl)benzene → (3,5-bis-trifluoromethyl-benzyl)-(2-bromo-5-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)amine

HRID 390740Notes

Reaction equation

HRID 390740 reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]1[CH:4]=[C:5]([CH:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:16]=1)[CH2:6][NH:7][C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.CC(C)([O-])C.[K+].[Br:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][C:31]=1[CH2:40]Br>C1COCC1>[F:18][C:17]([F:19])([F:20])[C:15]1[CH:14]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:21])[F:22])[CH:16]=1)[CH2:6][N:7]([CH2:40][C:31]1[CH:32]=[C:33]([C:36]([F:37])([F:39])[F:38])[CH:34]=[CH:35][C:30]=1[Br:29])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1

Participants

5

Reactant 3

HCID 27562491-Bromo-2-(bromomethyl)-4-(trifluoromethyl)benzeneHCID 230732215-[N-(3',5'-Bistrifluoromethylbenzyl)amino]-2-methyltetrazoleHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 58966468(3,5-bis-trifluoromethyl-benzyl)-(2-bromo-5-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)amineYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of N-(3,5-bis(trifluoromethyl)benzyl)-2-methyl-2H-tetrazol-5-amine (3.9 g, 12 mmol) in THF (50 mL) at room temperature was added potassium tert-butoxide (KOtBu) (13.2 ml of 1M solution, 13.2 mmol) followed by 1-bromo-2-(bromomethyl)-4-(trifluoromethyl)benzene (4 g, 12.6 mmol). The mixture was stirred at room temperature for 16 hours. Additional KOtBu in THF (13.2 mL of 1M solution, 13.2 mmol) was added and the mixture was stirred at room temperature for 2 hours. The reaction mixture was partitioned between water (50 mL) and ethyl acetate (3×50 mL). The combined organic layers were washed with saturated NaCl (50 mL), dried (MgSO4) and concentrated. The residue was purified by flash chromatography (silica gel) (eluted with 3:1 hexane-ethyl acetate) to yield the title compound (4.72 g). 1H NMR (400 MHz, CDCl3) δ 4.2 (s, 3 H) 4.8 (s, 2 H) 4.9 (s, 2 H) 7.4 (dd, J=8.2, 1.7 Hz, 1 H) 7.5 (d, J=1.7 Hz, 1 H) 7.7 (m, 3 H) 7.8 (s, 1 H). MS (ES+) Calc: 561.02, Found: 561.7 (M+1).

Workup

  1. stirringthe mixture was stirred at room temperature for 2 hours
  2. customThe reaction mixture was partitioned between water (50 mL) and ethyl acetate (3×50 mL)
  3. washThe combined organic layers were washed with saturated NaCl (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (silica gel) (eluted with 3:1 hexane-ethyl acetate)

Sources & evidence

ORD record
ord-ef9bdb9a75564fba8cdc2ea54fab9fb0
Source dataset
uspto-grants-2013_02
Patent number
US08383660B2

Reaction notes

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