Pyridine → 3-chloro-N-(2-fluorophenyl)propanamide

HRID 1922428Notes

Reaction equation

HRID 1922428 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].N1C=CC=CC=1.[Cl:15][CH2:16][CH2:17][C:18](Cl)=[O:19]>CC(C)=O.O.Cl>[Cl:15][CH2:16][CH2:17][C:18]([NH:4][C:3]1[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=1[F:1])=[O:19]

Participants

7

Reactant 3

HCID 1049PyridineHCID 95842-FluoroanilineHCID 693643-Chloropropionyl chloride

Product 1

HCID 42560293-chloro-N-(2-fluorophenyl)propanamide

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 313Hydrochloric AcidSolventHCID 962WaterSolvent

Procedure

2-Fluoroaniline (2 g, 17.99 mmol) was stirred in acetone (30 mL) and pyridine (2.91 mL, 35.99 mmol) and allowed to dissolve. To this solution was added 3-chloropropanoyl chloride (3.42 g, 26.99 mmol), slowly. The reaction mixture began to reflux, and when the mixture had cooled to room temperature (˜30 min) TLC analysis showed that the reaction was complete. The reaction mixture was then diluted with water and HCl(aq) (1N) and extracted with dichloromethane (3×). The combined organic extracts were dried over sodium sulfate, filtered and concentrated, then chromatographed on silica gel in 30% EtOAc in hexanes. Yield: 3.5 g, 97%. 1H NMR (CDCl3) δ 2.87 (t, 2H, J=6.7 Hz), 3.89 (t, 2H, J=6.7 Hz), 7.10 (m, 3H), 7.52 (brs, 1H), 8.30 (t, 1H, J=7.5 Hz). EI-MS (m/z, %): 201.1 (M+, 22), 111.1 (100).

Workup

  1. dissolutionto dissolve
  2. temperatureto reflux
  3. extractionextracted with dichloromethane (3×)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customchromatographed on silica gel in 30% EtOAc in hexanes

Sources & evidence

ORD record
ord-b82d4aea8bde4410b359bd820e2b82d7
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

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