Pyridine → HCID 59544195, compound

HRID 1037149Notes

Reaction equation

HRID 1037149 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:5]([NH:6][C:7]2[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[F:17][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][C:26]=1[O:27][CH3:28])[C:21](Cl)=[O:22].N1C=CC=CC=1>C1COCC1>[F:17][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][C:26]=1[O:27][CH3:28])[C:21]([N:6]([C:5]1[CH:15]=[CH:16][C:2]([F:1])=[CH:3][CH:4]=1)[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1)=[O:22]

Participants

5

Reactant 3

HCID 1049PyridineHCID 27792553-Fluoro-4-methoxybenzoyl chlorideHCID 12140011HCID 12140011, compound

Product 1

HCID 59544195HCID 59544195, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-Fluoro-N-(4-methoxyphenyl)aniline (1c) (90.78 g, 0.418 mol) and 3-fluoro-4-methoxybenzoyl chloride (94.55 g, 0.501 mol) were mixed together and dissolved in anhydrous THF (200 mL) in a dry 1 L three-necked round-bottomed flask fitted with a stifling bar, a reflux condenser and an argon inlet. Anhydrous pyridine (132.22 g, 1.672 mol) was added via a syringe at room temperature under argon. The reaction mixture was stirred and heated to reflux overnight. Then, the reaction mixture was cooled to room temperature and filtered to remove pyridine salt. The solution was concentrated to remove THF solvent. The residue oil was washed with 200 mL of 2N HCl solution and extracted with ethyl acetate (2×200 mL). The combined organic layer was washed with a saturated aqueous Na2CO3 solution (150 mL) to remove excess benzoyl chloride and acid, dried over MgSO4 (50 g), filtered, and concentrated under reduced pressure to give an oil. The residue was purified by flash column chromatography using silica-gel with CH2Cl2/acetone (50/1 v/v) to afford the pure corresponding benzamide compound as a yellow solid. M.p. 54-56° C. MS (ESI) m/z 370.1 [M+H]+, 1H NMR (CDCl3/TMS) δ 7.24-7.11 (m, 4H), 7.05-6.97 (m, 4H), 6.85-6.78 (m, 3H), 3.86 (s, 3H), 3.79 (s, 3H).

Workup

  1. customfitted with a stifling bar, a reflux condenser and an argon inlet
  2. temperatureheated
  3. temperatureto reflux overnight
  4. filtrationfiltered
  5. customto remove pyridine salt
  6. concentrationThe solution was concentrated
  7. customto remove THF solvent
  8. washThe residue oil was washed with 200 mL of 2N HCl solution
  9. extractionextracted with ethyl acetate (2×200 mL)
  10. washThe combined organic layer was washed with a saturated aqueous Na2CO3 solution (150 mL)
  11. customto remove excess benzoyl chloride and acid
  12. dry with materialdried over MgSO4 (50 g)
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customto give an oil
  16. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-265e06bdc1524b5eb1ffeba24293d467
Source dataset
uspto-grants-2013_10
Patent number
US08546451B2

Reaction notes

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