Acetyl chloride → 4-Chloro-3-(1-methylpiperidin-4-yl)aniline

HRID 1275004Notes

Reaction equation

HRID 1275004 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:9]=[C:10]([CH:12]=[CH:13][CH:14]=2)[NH2:11])[CH2:4][CH2:3]1.C(N(CC)CC)C.C([Cl:25])(=O)C.ClN1C(=O)CCC1=O.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.ClCCCl.O>[Cl:25][C:14]1[CH:13]=[CH:12][C:10]([NH2:11])=[CH:9][C:8]=1[CH:5]1[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]1

Participants

9

Reactant 5

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 31398ChlorosuccinimideHCID 223301453-(1-Methyl-4-piperidinyl)benzenamine

Product 1

HCID 221189274-Chloro-3-(1-methylpiperidin-4-yl)aniline

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-(1-methylpiperidin-4-yl)aniline (D6, 1.0 g, 5.3 mmol) in dichloromethane (50 ml) containing triethylarnine (1.1 ml, 7.9 mmol) was added dropwise acetyl chloride (0.40 ml, 5.6 mmol) and the mixture stirred at room temperature overnight. The mixture was washed with aqueous 10% sodium carbonate and the organics dried (Na2SO4), and evaporated in vacuo to a red semi-solid (1.49 g). To a solution of the solid in 1,2-dichloroethane (100 ml) was added N-chlorosuccinimide (1.2 g, 9.0 mmol) and the mixture heated at 80° C. for 28 h. On cooling, water (50 ml) was added and the aqueous basified with aqueous 10% sodium carbonate. The aqueous was extracted with dichloromethane (3×), the combined organics dried (Na2SO4). and evaporated in vacuo to a brown solid (650 mg). A stirred solution of the solid in ethanol (10 ml) and 2M NaOH (16 ml) was heated at reflux under argon for 18 h. The mixture was concentrated in vacuo, partitioned between ethyl acetate and water and the aqueous further extracted with ethyl acetate (3×). The combined organics were dried (Na2SO4) and evaporated in vacuo to the title compound as a pale brown solid (403 mg, 35%).

Workup

  1. washThe mixture was washed with aqueous 10% sodium carbonate
  2. dry with materialthe organics dried (Na2SO4)
  3. customevaporated in vacuo to a red semi-solid (1.49 g)
  4. temperaturethe mixture heated at 80° C. for 28 h
  5. temperatureOn cooling
  6. extractionThe aqueous was extracted with dichloromethane (3×)
  7. dry with materialthe combined organics dried (Na2SO4)
  8. customand evaporated in vacuo to a brown solid (650 mg)
  9. temperatureA stirred solution of the solid in ethanol (10 ml) and 2M NaOH (16 ml) was heated
  10. temperatureat reflux under argon for 18 h
  11. concentrationThe mixture was concentrated in vacuo
  12. custompartitioned between ethyl acetate and water
  13. extractionthe aqueous further extracted with ethyl acetate (3×)
  14. dry with materialThe combined organics were dried (Na2SO4)
  15. customevaporated in vacuo to the title compound as a pale brown solid (403 mg, 35%)

Sources & evidence

ORD record
ord-d101e9cd35f4481da4e17a281f79291f
Source dataset
uspto-grants-2000_12
Patent number
US06159979

Reaction notes

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