Sodium Carbonate → 2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-benzonitrile

HRID 2075101Notes

Reaction equation

HRID 2075101 reaction equation
Br[C:2]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][C:3]=1[CH2:4][N:5]([CH2:12][C:13]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[C:15](C(F)(F)F)[CH:14]=1)[C:6]1[N:7]=[N:8][N:9]([CH3:11])[N:10]=1.C(=O)([O-])[O-].[Na+].[Na+].C[N:42]([CH3:46])C(=O)C>C(OCC)C.[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.O.O.O.[K+].[K+].[K+].[Fe+3].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:21][C:19]([F:22])([F:20])[C:17]1[CH:18]=[C:13]([CH:14]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:16]=1)[CH2:12][N:5]([CH2:4][C:3]1[CH:27]=[C:28]([C:31]([F:33])([F:34])[F:32])[CH:29]=[CH:30][C:2]=1[C:46]#[N:42])[C:6]1[N:7]=[N:8][N:9]([CH3:11])[N:10]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 31374DimethylacetamideHCID 58966468(3,5-bis-trifluoromethyl-benzyl)-(2-bromo-5-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)amine

Product 1

HCID 589664932-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-benzonitrileYield 89.9%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 71306920Tripotassium;iron(3+);hexacyanide;trihydrateCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of N-(2-bromo-5-(trifluoromethyl)benzyl)-N-(3,5-bis(trifluoromethyl)benzyl)-2-methyl-2H-tetrazol-5-amine (10.4 g; 18.5 mmol), potassium hexacyanoferrate trihydrate (1.9 G; 4.49 mmol) and sodium carbonate (2.4 g; 22.6 mmol) was stirred in N,N-dimethylacetamide (32 mL). Palladium acetate was added (0.48 g; 2.13 mmol). The reaction was stirred at 120° C. for 16 hours. The reaction was diluted with diethyl ether and filtered over a pad of silica gel and celite. The mother liquor was washed with water (3×) and brine. It was dried over sodium sulfate and concentrated under reduced pressure. The crude was purified over a 330 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 10-30% ethyl acetate in heptane) to give 8.45 g (89.9%) of title compound as a tan solid. MS (ES+): Calc: 508.3, Found: 509.2 (M+H). 1H NMR (400 MHz, CDCl3) δ ppm 7.76 (s, 1H), 7.75 (d, J=8.30 Hz, 1H), 7.68 (s, 3H), 7.62 (dd, J=8.30 Hz, 1H), 4.96 (s, 2H), 4.89 (s, 2H), 4.22 (s, 3H).

Workup

  1. filtrationfiltered over a pad of silica gel and celite
  2. washThe mother liquor was washed with water (3×) and brine
  3. dry with materialIt was dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude was purified over a 330 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 10-30% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-1a77315e1a8b4d8c8f5c869582178334
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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