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

HRID 1163891Notes

Reaction equation

HRID 1163891 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]([NH:40][CH3:41])[CH2:36][CH2:35]2)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1.C(=O)(O)[O-].[Na+]>O1CCCC1.CN(C)C=O>[CH3:41][N:40]([CH:37]1[CH2:36][CH2:35][N:34]([CH2:33][CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[CH2:39][CH2:38]1)[C:18](=[O:20])[C:17]1[CH:21]=[C:22]([Cl:26])[C:23]([NH2:25])=[CH:24][C:16]=1[O:15][CH3:14]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 816264-Amino-5-chloro-2-methoxybenzoic acidHCID 516892Sodium BicarbonateHCID 205132771-Cyclohexylmethyl-4-methylaminopiperidine

Product 1

HCID 15572451N-methyl-N-(1-cyclohexylmethylpiperid-4-yl)-2-methoxy-4-amino-5-chlorobenzamideYield 81.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

Triethylamine (4.2 ml; 0.03 moles) and a solution of ethyl chloroformate (2.85 ml; 0.03 moles) in anhydrous tetrahydrofuran (35 ml) were added successively to a solution of 2-methoxy-4-amino-5-chlorobenzoic acid (6.04 g; 0.03 moles) in N,N-dimethylformamide (225 ml) whilst maintaining the temperature at -10° C. After stirring at this temperature for 2 hours, a solution of 1-cyclohexylmethyl-4-methylaminopiperidine (6.15 g; 0.03 moles) in anhydrous tetrahydrofuran (35 ml) was added, and the temperature was allowed overnight to reach room temperature. The mixture was poured into an aqueous solution of sodium bicarbonate, extracted with chloroform and the organic layers washed with water. The chloroformic solution was dried (Na2SO4) and the solvent removed in vacuo to give a solid which was recrystallized from a mixture of ethanol and diethyl ether. N-methyl-N-(1-cyclohexylmethylpiperid-4-yl)-2-methoxy-4-amino-5-chlorobenzamide (9.6 g) was obtained.

Workup

  1. waitthe temperature was allowed overnight
  2. customto reach room temperature
  3. extractionextracted with chloroform
  4. washthe organic layers washed with water
  5. dry with materialThe chloroformic solution was dried (Na2SO4)
  6. customthe solvent removed in vacuo
  7. customto give a solid which
  8. customwas recrystallized from a mixture of ethanol and diethyl ether

Sources & evidence

ORD record
ord-943861c7e4b8418b94255c24ac88d3af
Source dataset
uspto-grants-1983_01
Patent number
US04367232

Reaction notes

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