Pyridine → HCID 23516247, compound

HRID 1793000Notes

Reaction equation

HRID 1793000 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:18]([F:19])=[C:17]([F:20])[CH:16]=[CH:15][C:11]=1[C:12]([OH:14])=[O:13].N1C=CC=CC=1.FC(F)(F)C(O[C:32]1[C:37]([F:38])=[C:36]([F:39])[C:35]([F:40])=[C:34]([F:41])[C:33]=1[F:42])=O>CN(C)C=O.C(OCC)(=O)C>[F:38][C:37]1[C:32]([O:13][C:12](=[O:14])[C:11]2[CH:15]=[CH:16][C:17]([F:20])=[C:18]([F:19])[C:10]=2[NH:9][C:3]2[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=2[Cl:1])=[C:33]([F:42])[C:34]([F:41])=[C:35]([F:40])[C:36]=1[F:39]

Participants

6

Reactant 3

HCID 1049PyridineHCID 4327891Pentafluorophenyl TrifluoroacetateHCID 101121912-(2-chloro-4-iodophenylamino)-3,4-difluorobenzoic acid2×

Product 1

HCID 23516247HCID 23516247, compoundYield 91%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the product of Example 2, Step A, 2-(2-chloro-4-iodophenylamino)-3,4-difluorobenzoic acid (10.0 g, 24.4 mmol), and pyridine (2.16 mL, 26.8 mmol) in anhydrous dimethylformamide (49 mL) was added pentafluorophenyl trifluoroacetate (5.35 mL, 30.5 mmol). The resultant solution was stirred at ambient temperature for 2 hours. The reaction mixture was diluted with ethyl acetate (600 mL) and washed with 0.1 M aqueous hydrochloric acid (2×240 mL), 25% saturated aqueous sodium bicarbonate (2×240 mL), and saturated brine (240 mL). The organics were dried over anhydrous magnesium sulfate and concentrated under reduced pressure to afford an oil that was purified on silica gel. Elution with hexanes-ethyl acetate (19:1) afforded 2-(2-chloro-4-iodophenylamino)-3,4-difluorobenzoic acid pentafluorophenyl ester (12.8 g, 91%) as a pale-yellow powder: m.p. 108.5–110.0° C.; 1H-NMR (400 MHz, CDCl3) δ 8.77 (br s, 1 H), 8.07 (br s, 1 H), 7.69 (br s, 1 H), 7.48 (br d, J=7.0 Hz, 1 H), 6.91 (br d, J=7.2 Hz, 1 H), 6.67 (br s., 1 H); 19F-NMR (376 MHz, CDCl3) δ −123.74 (s, 1F), −139.17 (d, J=16.8 Hz, 1F), −152.35 (d, J=21.4 Hz, 2F), −156.96 (t, J=21.4 Hz, 1F), −161.81 (t, J=21.4 Hz, 2F). Anal. Calcd/found for C19H6NO2F7ClI: C, 39.65/39.32; H, 1.05/0.91; N, 2.43/2.35; F, 23.10/22.85; Cl, 6.16/6.92; I, 22.05/22.50.

Workup

  1. washwashed with 0.1 M aqueous hydrochloric acid (2×240 mL), 25% saturated aqueous sodium bicarbonate (2×240 mL), and saturated brine (240 mL)
  2. dry with materialThe organics were dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto afford an oil that
  5. customwas purified on silica gel
  6. washElution with hexanes-ethyl acetate (19:1)

Sources & evidence

ORD record
ord-899d1d4e9b5d4a96af3a362160180f80
Source dataset
uspto-grants-2006_07
Patent number
US07078438B2

Reaction notes

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