N-Methylaniline → HCID 18543869, compound

HRID 649846Notes

Reaction equation

HRID 649846 reaction equation
C([Li])CCC.[CH3:6][NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[Cl:14][C:15]1[CH:16]=[C:17]([N+:22]([O-:24])=[O:23])[CH:18]=[CH:19][C:20]=1F>O1CCCC1>[Cl:14][C:15]1[CH:16]=[C:17]([N+:22]([O-:24])=[O:23])[CH:18]=[CH:19][C:20]=1[N:7]([CH3:6])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 7515N-MethylanilineHCID 676882-Chloro-1-fluoro-4-nitrobenzeneHCID 178418339Butyllithium

Product 1

HCID 18543869HCID 18543869, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

n-Butyl lithium (12.3 mL of a 2.5 M solution in hexanes) is added dropwise to a solution of N-methyl aniline (3.0 g) in tetrahydrofuran (75 mL) at 0° C. The mixture is allowed to warm slowly to room temperature and is then re-cooled to 0° C. and added by cannula to a solution of 3-chloro-4-fluoronitrobenzene (4.9 g) in tetrahydrofuran (35 mL) that is kept at −78° C. Following the addition, the reaction mixture is permitted to warm to room temperature over the course of 1 hour, and is then concentrated under reduced pressure, quenched by addition of saturated aqueous ammonium chloride, and extracted three times with ethyl acetate. The pooled organic layers are washed three times with 5% aqueous hydrochloric acid, once with water, once with saturated aqueous sodium bicarbonate, once with saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. Following removal of the solvent under reduced pressure the residue is chromatographed over silica gel (5% diethyl ether in hexanes is used as the eluant) to provide the desired product as a clear colorless oil.

Workup

  1. temperatureis then re-cooled to 0° C.
  2. customis kept at −78° C
  3. additionthe addition
  4. temperatureto warm to room temperature over the course of 1 hour
  5. concentrationis then concentrated under reduced pressure
  6. customquenched by addition of saturated aqueous ammonium chloride
  7. extractionextracted three times with ethyl acetate
  8. washThe pooled organic layers are washed three times with 5% aqueous hydrochloric acid
  9. dry with materialonce with water, once with saturated aqueous sodium bicarbonate, once with saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate
  10. customremoval of the solvent under reduced pressure the residue
  11. customis chromatographed over silica gel (5% diethyl ether in hexanes

Sources & evidence

ORD record
ord-d4cffcac2bfe460ab9cd387a76354d8c
Source dataset
uspto-grants-2001_08
Patent number
US06271236B1

Reaction notes

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