Citric Acid → (3,5-bis-trifluoromethyl-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-(2H-tetrazol-5-yl)-amine

HRID 604141Notes

Reaction equation

HRID 604141 reaction equation
[F:1][C:2]([F:40])([F:39])[C:3]1[CH:4]=[C:5]([CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1)[CH2:6][N:7]([CH2:10][C:11]1[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[CH:13][C:12]=1[C:21]1[CH:26]=[C:25]([CH:27]([CH3:29])[CH3:28])[CH:24]=[CH:23][C:22]=1[O:30][CH3:31])[C:8]#[N:9].[N-:41]=[N+:42]=[N-:43].[Na+].[Cl-].[NH4+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O>[F:1][C:2]([F:39])([F:40])[C:3]1[CH:4]=[C:5]([CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1)[CH2:6][N:7]([CH2:10][C:11]1[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[CH:13][C:12]=1[C:21]1[CH:26]=[C:25]([CH:27]([CH3:28])[CH3:29])[CH:24]=[CH:23][C:22]=1[O:30][CH3:31])[C:8]1[N:41]=[N:42][NH:43][N:9]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 86626887(3,5-Bis-trifluoromethyl-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-cyanamide

Product 1

HCID 86626888(3,5-bis-trifluoromethyl-benzyl)-(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-(2H-tetrazol-5-yl)-amineYield 98.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

(3,5-Bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-cyanamide (1.8 g) is dissolved in N,N-dimethylformamide (10 ml), and thereto are added sodium azide (407 mg) and ammonium chloride (335 mg), and the mixture is heated to 100° C. and stirred for 6 hours. The reaction solution is allowed to cool to room temperature, and thereto is added a 10% aqueous citric acid solution and the mixture is extracted with ethyl acetate. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (chloroform:methanol=30:1) to give (3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-(2H-tetrazol-5-yl)-amine (1.9 g). MS (m/z): 618 [M+H]+

Workup

  1. temperatureto cool to room temperature
  2. extractionthe mixture is extracted with ethyl acetate
  3. washThe organic layer is washed with a saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue is purified by silica gel column chromatography (chloroform:methanol=30:1)

Sources & evidence

ORD record
ord-efba95fedaef4f8593b2670efb651824
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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