Benzophenone imine → 6-Methoxy-5-(trifluoromethyl)pyridin-3-amine

HRID 1812395Notes

Reaction equation

HRID 1812395 reaction equation
I[C:2]1[CH:3]=[C:4]([C:10]([F:13])([F:12])[F:11])[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C1(C(C2C=CC=CC=2)=[NH:63])C=CC=CC=1.CC([O-])(C)C.[Na+]>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN(C=O)C>[CH3:9][O:8][C:5]1[N:6]=[CH:7][C:2]([NH2:63])=[CH:3][C:4]=1[C:10]([F:13])([F:12])[F:11]

Participants

8

Reactant 4

HCID 136809Benzophenone imineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 116880685-Iodo-2-methoxy-3-(trifluoromethyl)pyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 666004856-Methoxy-5-(trifluoromethyl)pyridin-3-amineYield 34%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To 5-Iodo-2-methoxy-3-(trifluoromethyl)pyridine (0.97 g, 3.20 mmol) (ECA International Product List) was added DMF (8.0 mL), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.093 g, 0.160 mmol), Pd2(dba)3 (0.147 g, 0.160 mmol), diphenylmethanimine (0.806 mL, 4.80 mmol), and sodium 2-methylpropan-2-olate (1.231 g, 12.80 mmol), and the resulting mixture was heated at 120° C. for 30 min. The reaction mixture was then diluted with 100 mL of EtOAc, added to a separatory funnel, partitioned with 1 N HCl (aqueous), and washed 2 times with 50 mL of sodium bicarbonate (saturated, aqueous). The organic layer was separated, dried over sodium sulfate, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0% to 5% (2 M ammonia in MeOH)/DCM) provided the title compound (34% yield). m/z (ESI, +ve ion) 193.2 (M+H)+.

Workup

  1. additionadded to a separatory funnel
  2. custompartitioned with 1 N HCl (aqueous)
  3. washwashed 2 times with 50 mL of sodium bicarbonate (saturated, aqueous)
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customChromatographic purification of the residue (silica gel, 0% to 5% (2 M ammonia in MeOH)/DCM)

Sources & evidence

ORD record
ord-2aa369e77bd54687a5db351182165e64
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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