Hydroxylamine HCl → 1-[5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamine

HRID 604147Notes

Reaction equation

HRID 604147 reaction equation
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:22][CH3:23])=[C:8]([C:10]2[C:11]([CH:20]=O)=[CH:12][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:14][CH:15]=2)[CH:9]=1)([CH3:3])[CH3:2].[Cl-].O[NH3+:26].C([O-])(=O)C.[Na+]>C(O)C>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:22][CH3:23])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=2[CH2:20][NH2:26])[CH:9]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 21645Hydroxylamine HClHCID 517045Sodium AcetateHCID 578779885'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-carbaldehyde

Product 1

HCID 591351271-[5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamineYield 52.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

5′-Isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-carbaldehyde (3.00 g) is dissolved in ethanol (40 ml) and thereto are added hydroxyl ammonium chloride (1.29 g) and sodium acetate (1.53 g), and the mixture is stirred under nitrogen atmosphere at 60° C. for 1 hour and a half. The reaction solution is concentrated under reduced pressure, and thereto is added a saturated brine, 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 (3.3 g) is dissolved in methanol (40 ml), and thereto is added Raney nickel (5 g) and the mixture is stirred under hydrogen atmosphere at room temperature overnight. Raney nickel is removed by filtration and the filtrate is concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (chloroform:methanol=1:0→19:1) to give C-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-yl)-methylamine (1.57 g). MS (m/z): 324 [M+H]+

Workup

  1. concentrationThe reaction solution is concentrated under reduced pressure
  2. additionis added a saturated brine
  3. extractionthe mixture is extracted with ethyl acetate
  4. washThe organic layer is washed with a saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe resulting residue (3.3 g) is dissolved in methanol (40 ml)
  8. additionis added Raney nickel (5 g)
  9. stirringthe mixture is stirred under hydrogen atmosphere at room temperature overnight
  10. customRaney nickel is removed by filtration
  11. concentrationthe filtrate is concentrated under reduced pressure
  12. customThe resulting residue is purified by silica gel column chromatography (chloroform:methanol=1:0→19:1)

Sources & evidence

ORD record
ord-817a6c6da4864bed84957c66116bc592
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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