Ethyl Acetate → 2,3,5-trifluoro-N-(2-fluoro-4-iodophenyl)-6-nitroaniline

HRID 1914864Notes

Reaction equation

HRID 1914864 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[F:11][C:12]1[CH:18]=[C:17]([I:19])[CH:16]=[CH:15][C:13]=1[NH2:14].F[C:21]1[C:26]([F:27])=[C:25]([F:28])[CH:24]=[C:23]([F:29])[C:22]=1[N+:30]([O-:32])=[O:31].C(OCC)(=O)C>C1COCC1.CCCCCC>[F:11][C:12]1[CH:18]=[C:17]([I:19])[CH:16]=[CH:15][C:13]=1[NH:14][C:21]1[C:22]([N+:30]([O-:32])=[O:31])=[C:23]([F:29])[CH:24]=[C:25]([F:28])[C:26]=1[F:27]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 675661,2,3,5-Tetrafluoro-4-nitrobenzeneHCID 1856942-Fluoro-4-iodoanilineHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 574300722,3,5-trifluoro-N-(2-fluoro-4-iodophenyl)-6-nitroanilineYield 58.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

1.0M LHMDS in hexane (153 mL, 153 mol) was added drop wise to a solution of 2-fluoro-4-iodoaniline (30.0 g, 128 mol) in dry THF (600 mL) at −78° C. over a period of 30 minutes and the resulting mixture was stirred at −78° C. for 30 minutes. This was followed by the addition of 2,3,4,6-tetrafluoronitrobenzene (25 g, 128 mol) in dry THF (150 mL) and stirring was continued for a further 1 hour at room temperature. The reaction was monitored by TLC (10% ethyl acetate in hexane). The reaction mixture was quenched with 2N HCl (100 mL), concentrated and the concentrate was partitioned between water (500 mL) and ethyl acetate (300 mL). The aqueous layer was washed with ethyl acetate (2×200 mL). The combined organic phase was washed with water, brine solution, dried over anhydrous Na2SO4 and concentrated to afford 38 g of the crude product. Purification by column chromatography on silica gel (0-5% ethyl acetate in hexane) afforded 31 g of the product (58.8% yield). LCMS: 95.5%, m/z=410.9 (M−1).

Workup

  1. stirringstirring
  2. waitwas continued for a further 1 hour at room temperature
  3. customThe reaction mixture was quenched with 2N HCl (100 mL)
  4. concentrationconcentrated
  5. customthe concentrate was partitioned between water (500 mL) and ethyl acetate (300 mL)
  6. washThe aqueous layer was washed with ethyl acetate (2×200 mL)
  7. washThe combined organic phase was washed with water, brine solution
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationconcentrated
  10. customto afford 38 g of the crude product
  11. customPurification by column chromatography on silica gel (0-5% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-971ae82f9cf749f496a08dd829fdb853
Source dataset
uspto-grants-2013_12
Patent number
US08614239B2

Reaction notes

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