Triethylamine → N-(1-Cyclohexylmethylpiperid-4-yl)-2-methoxy-4-amino-5-chlorobenzamide

HRID 261050Notes

Reaction equation

HRID 261050 reaction equation
C(N(CC)CC)C.ClC(OCC)=O.[CH3:14][O:15][C:16]1[CH:24]=[C:23]([NH2:25])[C:22]([Cl:26])=[CH:21][C:17]=1[C:18]([OH:20])=O.[CH:27]1([CH2:33][N:34]2[CH2:39][CH2:38][CH:37]([NH2:40])[CH2:36][CH2:35]2)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>O1CCCC1>[CH:27]1([CH2:33][N:34]2[CH2:39][CH2:38][CH:37]([NH:40][C:18](=[O:20])[C:17]3[CH:21]=[C:22]([Cl:26])[C:23]([NH2:25])=[CH:24][C:16]=3[O:15][CH3:14])[CH2:36][CH2:35]2)[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 816264-Amino-5-chloro-2-methoxybenzoic acidHCID 64969411-(Cyclohexylmethyl)piperidin-4-amine

Product 1

HCID 20395834N-(1-Cyclohexylmethylpiperid-4-yl)-2-methoxy-4-amino-5-chlorobenzamideYield 52.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Triethylamine (5.6 ml; 0.04 moles) and ethyl chloroformate (3.84 ml; 0.04 moles) were added successively to a stirred suspension of 2-methoxy-4-amino-5-chlorobenzoic acid (8 g; 0.04 moles) in anhydrous tetrahydrofuran (300 ml) whilst maintaining the temperature beween -5° and -10° C. After stirring at this temperature for 0.5 hours, a solution of 1-cyclohexylmethyl-4-aminopiperidine (7.85 g; 0.04 moles) in anhydrous tetrahydrofuran (50 ml) was added, the temperature was maintained at -5° to -10° C. for 1 hour and then allowed overnight to reach room temperature. The solvent of the mixture was removed in vacuo, the residue poured into water, extracted with chloroform and the organic layer washed with water. The chloroformic solution was dried (Na2SO4) and the solvent removed in vacuo to give a solid which was triturated with a mixture of methanol and diethyl ether. N-(1-Cyclohexylmethylpiperid-4-yl)-2-methoxy-4-amino-5-chlorobenzamide (8 g) was thus obtained.

Workup

  1. temperaturewhilst maintaining the temperature beween -5°
  2. custom-10° C
  3. temperaturethe temperature was maintained at -5° to -10° C. for 1 hour
  4. waitallowed overnight
  5. customto reach room temperature
  6. customThe solvent of the mixture was removed in vacuo
  7. additionthe residue poured into water
  8. extractionextracted with chloroform
  9. washthe organic layer washed with water
  10. dry with materialThe chloroformic solution was dried (Na2SO4)
  11. customthe solvent removed in vacuo
  12. customto give a solid which
  13. customwas triturated with a mixture of methanol and diethyl ether

Sources & evidence

ORD record
ord-dd76bdcced23472c99272637b82766ce
Source dataset
uspto-grants-1979_08
Patent number
US04163789

Reaction notes

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