2-Fluoro-4-iodoaniline → (2-Dimethoxymethyl-3-fluoro-5-methoxy-6-nitro-phenyl)-(2-fluoro-4-iodo-phenyl)-amine

HRID 79044Notes

Reaction equation

HRID 79044 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH2:9].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:20][O:21][CH:22]([O:36][CH3:37])[C:23]1[C:28](F)=[C:27]([N+:30]([O-:32])=[O:31])[C:26]([O:33][CH3:34])=[CH:25][C:24]=1[F:35]>C1COCC1>[CH3:37][O:36][CH:22]([O:21][CH3:20])[C:23]1[C:24]([F:35])=[CH:25][C:26]([O:33][CH3:34])=[C:27]([N+:30]([O-:32])=[O:31])[C:28]=1[NH:9][C:3]1[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=1[F:1]

Participants

5

Reactant 3

HCID 1856942-Fluoro-4-iodoanilineHCID 2733832Lithium HexamethyldisilazideHCID 58374324HCID 58374324, compound

Product 1

HCID 86656239(2-Dimethoxymethyl-3-fluoro-5-methoxy-6-nitro-phenyl)-(2-fluoro-4-iodo-phenyl)-amineYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cold (−78° C.) solution of 2-fluoro-4-iodo-phenyl amine (2.97 g, 12.5 mmol) in THF (20 mL) was added LHMDS (24 mL, 1.0 M solution in hexanes 24 mmol) dropwise maintaining the temperature below −65° C. After stirring for 30 minutes a solution of 2-dimethoxymethyl-1,3-difluoro-5-methoxy-4-nitro-benzene (3.0 g, 11.4 mmol) in THF (20 mL) was added dropwise, the resultant mixture stirred cold (−78° C.) for 1 hour then allowed to warm to room temperature and stirred for 18 hours. The reaction was quenched by the addition of aqueous ammonium chloride and extracted twice with diethyl ether. The combined organic extracts were washed with water, dried (Na2SO4), filtered and concentrated in vacuo to give an orange solid. The crude orange solid was triturated in diethyl ether to give the title compound as a yellow solid (4.2 g, 77%). 1H NMR (CDCl3) 7.36 (1 H, dd, J=10.09, 1.93 Hz), 7.28-7.17 (2 H, m), 6.59 (1 H, t, J=8.62 Hz), 6.44 (1H, d, J=11.47 Hz), 5.49 (1 H, s), 3.88 (3 H, s), 3.39 (6 H, s).

Workup

  1. temperaturedropwise maintaining the temperature below −65° C
  2. additionwas added dropwise
  3. customThe reaction was quenched by the addition of aqueous ammonium chloride
  4. extractionextracted twice with diethyl ether
  5. washThe combined organic extracts were washed with water
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give an orange solid
  10. customThe crude orange solid was triturated in diethyl ether

Sources & evidence

ORD record
ord-db06df38e0684729a8126a858fdb9c1e
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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