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

HRID 1914889

Reaction equation

HRID 1914889 reaction equation
[CH2:1]([O:3][CH:4]([O:7][CH2:8][CH3:9])[CH2:5][OH:6])[CH3:2].[H-].[Na+].[F:12][C:13]1[CH:18]=[C:17]([I:19])[CH:16]=[CH:15][C:14]=1[NH:20][C:21]1[C:26]([N+:27]([O-:29])=[O:28])=[C:25](F)[CH:24]=[C:23]([F:31])[C:22]=1[F:32].C(OCC)(=O)C>C1COCC1.CCCCCC>[CH2:1]([O:3][CH:4]([O:7][CH2:8][CH3:9])[CH2:5][O:6][C:25]1[C:26]([N+:27]([O-:29])=[O:28])=[C:21]([C:22]([F:32])=[C:23]([F:31])[CH:24]=1)[NH:20][C:14]1[CH:15]=[CH:16][C:17]([I:19])=[CH:18][C:13]=1[F:12])[CH3:2]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 121292,2-DiethoxyethanolHCID 24758Sodium hydrideHCID 574300722,3,5-trifluoro-N-(2-fluoro-4-iodophenyl)-6-nitroaniline

Product 1

HCID 866714883-(2,2-Diethoxyethoxy)-5,6-difluoro-N-(2-fluoro-4-iodophenyl)-2-nitroanilineYield 47%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
30 °C

Procedure

2,2-Diethoxy-ethanol (0.209 g, 1.2135 mmol) was added to a cooled suspension of NaH (0.034 g, 1.456 mmol) in THF (5 mL) at 0° C. and the resulting mixture was stirred for 30 minutes at 20-40° C. 2-Fluoro-4-iodo-phenyl-(2,3,5-trifluoro-6-nitro-phenyl)-amine (0.5 g, 1.2135 mmol) in THF (10 mL) was added slowly to the reaction mass at 0° C. and stirring was continued for a further 15 minutes. The reaction mass was stirred overnight at room temperature. The reaction was monitored by TLC (20% ethyl acetate in hexane). The reaction mass was concentrated under reduced pressure and the concentrate was extracted with ethyl acetate. The organic layer was washed with water, brine solution, dried over sodium sulphate and concentrated under reduced pressure to afford the crude compound. Purification by column chromatography on silica gel (15% ethyl acetate in hexane) afforded 0.3 g of the product (47% yield). 1H NMR (CDCl3, 300 MHz): δ 7.42 (d, 1H), 7.35 (d, 1H), 6.90 (bs, 1H), 6.58-6.68 (m, 2H), 4.58 (t, 1H), 4.15 (d, 2H), 3.51-3.80 (m, 4H), 1.22 (t, 6H).

Workup

  1. stirringstirring
  2. waitwas continued for a further 15 minutes
  3. stirringThe reaction mass was stirred overnight at room temperature
  4. concentrationThe reaction mass was concentrated under reduced pressure
  5. extractionthe concentrate was extracted with ethyl acetate
  6. washThe organic layer was washed with water, brine solution
  7. dry with materialdried over sodium sulphate
  8. concentrationconcentrated under reduced pressure
  9. customto afford the crude compound
  10. customPurification by column chromatography on silica gel (15% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-413331fa93e04ec18b9b9c3d2bd450f5
Source dataset
uspto-grants-2013_12
Patent number
US08614239B2

Linked notes

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