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

HRID 1914866Notes

Reaction equation

HRID 1914866 reaction equation
C[O-].[Na+].[F:4][C:5]1[CH:10]=[C:9]([I:11])[CH:8]=[CH:7][C:6]=1[NH:12][C:13]1[C:18]([N+:19]([O-:21])=[O:20])=[C:17](F)[CH:16]=[C:15]([F:23])[C:14]=1[F:24].[C:25](OCC)(=[O:27])C>C1COCC1.CCCCCC>[F:24][C:14]1[C:15]([F:23])=[CH:16][C:17]([O:27][CH3:25])=[C:18]([N+:19]([O-:21])=[O:20])[C:13]=1[NH:12][C:6]1[CH:7]=[CH:8][C:9]([I:11])=[CH:10][C:5]=1[F:4]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 10942334Sodium MethoxideHCID 574300722,3,5-trifluoro-N-(2-fluoro-4-iodophenyl)-6-nitroaniline

Product 1

HCID 593863122,3-Difluoro-N-(2-fluoro-4-iodophenyl)-5-methoxy-6-nitroanilineYield 70.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

A mixture of sodium methoxide (32.0 g, 600 mmol) in dry THF (500 mL) at −78° C. was added to (2-fluoro-4-iodo-phenyl)-(2,3,5-trifluoro-6-nitro-phenyl)-amine (25 g, 60 mmol) and the resulting mixture was stirred at room temperature overnight. The reaction was monitored by TLC (20% ethyl acetate in hexane). The reaction mixture was quenched with 200 mL of water and concentrated. The concentrate was acidified with cold 2N HCl (pH=2) and extracted with ethyl acetate (200 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated to afford the crude product. Purification by column chromatography on silica gel (1-5% ethyl acetate in hexane) afforded 18 g of the product (70.6% yield). H1NMR (CDCl3, 300 MHz): δ 7.42 (dd, 1H), 7.34 (d, 1H), 6.9 (s, 1H), 6.64-6.54 (m, 2H), 3.92 (s, 3H). LCMS: 94.1%, m/z=422.9 (M−1). HPLC: 98.8%.

Workup

  1. customThe reaction mixture was quenched with 200 mL of water
  2. concentrationconcentrated
  3. extractionextracted with ethyl acetate (200 mL×3)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customto afford the crude product
  8. customPurification by column chromatography on silica gel (1-5% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-6b11582f149c4cdfa268c3f428c81fde
Source dataset
uspto-grants-2013_12
Patent number
US08614239B2

Reaction notes

Loading…