3-chloro-N-(diphenylmethylene)-4-(2-fluoro-4-nitrophenoxy)pyridin-2-amine → 4-(4-amino-2-fluorophenoxy)-3-chloro-N-(diphenylmethylene)pyridin-2-amine

HRID 408031Notes

Reaction equation

HRID 408031 reaction equation
[Cl:1][C:2]1[C:3]([N:19]=[C:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][C:10]=1[F:18].N#N.[H][H].[H][H]>[Ni]>[NH2:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][C:7]2[CH:6]=[CH:5][N:4]=[C:3]([N:19]=[C:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:2]=2[Cl:1])=[C:10]([F:18])[CH:11]=1

Participants

5

Reactant 3

HCID 581336033-chloro-N-(diphenylmethylene)-4-(2-fluoro-4-nitrophenoxy)pyridin-2-amineHCID 178418361HCID 178418361, compound3×HCID 178514468HCID 178514468, compound

Product 1

HCID 581336014-(4-amino-2-fluorophenoxy)-3-chloro-N-(diphenylmethylene)pyridin-2-amineYield 95.2%

Reagents, catalysts & solvents 1

HCID 935NickelCatalyst

Conditions

Temperature
90 °C

Procedure

To a reactor was added 10 g of 3-Chloro-N-(diphenylmethylene)-4-(2-fluoro-4-nitrophenoxy)pyridin-2-amine, 1.4 g of Ra-Nickel (type A-5001 from Johnson Matthay) and 100 mL of Me-THF. The reactor was inerted by three nitrogen/hydrogen swings, then pressurized to 25 psig with hydrogen. The reaction mixture was stirred under 25 psig of hydrogen at 25° C. until the hydrogen uptake ceased (1.6 L consumed) and the reaction was judged complete by HPLC. BuOAc (50 mL) was added to the reaction mixture and MeTHF was distilled off under atmospheric pressure until <1% of Me-THF were detected by GC. Maintaining a batch temperature of 90° C., heptane (50 mL) was added over 20 min. The solution was then allowed to cool to room temperature over 8 hrs. The solids were filtered off and the cake was washed with 50 mL heptane. The solid was dried in a vacuum oven at 60° C. for 12 hr to afford 4-(4-Amino-2-fluorophenoxy)-3-chloro-N-(diphenylmethylene)pyridin-2-amine (8.88 g; 95% yield) as a light yellow crystalline solid.

Workup

  1. custom(1.6 L consumed)
  2. additionBuOAc (50 mL) was added to the reaction mixture and MeTHF
  3. distillationwas distilled off under atmospheric pressure until <1% of Me-THF
  4. additionwas added over 20 min
  5. temperatureto cool to room temperature over 8 hrs
  6. filtrationThe solids were filtered off
  7. washthe cake was washed with 50 mL heptane
  8. customThe solid was dried in a vacuum oven at 60° C. for 12 hr

Sources & evidence

ORD record
ord-a94925710fbc4e0a91275302ed4ad887
Source dataset
uspto-grants-2014_06
Patent number
US08754230B2

Reaction notes

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