Pyridine → N-Methoxy-N-methyl-5,6-dimethoxy-3-phenyl-1,2,3,4-tetrahydro-naphthalene-1-carboxamide

HRID 1089025Notes

Reaction equation

HRID 1089025 reaction equation
[CH3:1][O:2][C:3]1[C:12]([O:13][CH3:14])=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH:6]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:7][CH:8]2[C:15](O)=[O:16].C(Cl)(=O)C(Cl)=O.Cl.[CH3:31][NH:32][O:33][CH3:34].N1C=CC=CC=1>C1(C)C=CC=CC=1.C(O)C>[CH3:34][O:33][N:32]([CH3:31])[C:15]([CH:8]1[C:9]2[C:4](=[C:3]([O:2][CH3:1])[C:12]([O:13][CH3:14])=[CH:11][CH:10]=2)[CH2:5][CH:6]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:7]1)=[O:16]

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 199611505,6-Dimethoxy-3-phenyl-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid

Product 1

HCID 19961165N-Methoxy-N-methyl-5,6-dimethoxy-3-phenyl-1,2,3,4-tetrahydro-naphthalene-1-carboxamideYield 98%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

5,6-Dimethoxy-3-phenyl-1,2,3,4-tetrahydro 1-naphthalene carboxylic acid (5 g, 16 mmol), from Step 3, was suspended in 100 mL of toluene and 5 mL of oxalyl chloride was added. The reaction mixture was heated at reflux temperature for 1.5 h under a nitrogen atmosphere. The solvent was evaporated and the water removed from the residue as an azeotrope with toluene (2×40 mL). The acid chloride and 2 g (20 mmol) of N,O-dimethylhydroxylamine hydrochloride were dissolved in 80 mL of ethanol free chloroform. The solution was cooled to 0° C. and 3.3 mL of pyridine was added slowly. The reaction mixture was allowed to warm to ambient temperature and stirred at ambient temperature for approximately 4 h then evaporated to dryness. The residue was dissolved in a 1:1 mixture of diethyl ether and methylene chloride and washed with brine. The layers were separated and the organic layer dried over magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound as an oil in 98% yield. The product of Step 4 was used in the next step without purification.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux temperature for 1.5 h under a nitrogen atmosphere
  3. customThe solvent was evaporated
  4. customthe water removed from the residue as an azeotrope with toluene (2×40 mL)
  5. temperatureto warm to ambient temperature
  6. customthen evaporated to dryness
  7. dissolutionThe residue was dissolved in a 1:1 mixture of diethyl ether and methylene chloride
  8. washwashed with brine
  9. customThe layers were separated
  10. dry with materialthe organic layer dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-3cef15bc82c8478dbff020c49aa2b1ad
Source dataset
uspto-grants-1990_10
Patent number
US04963568

Reaction notes

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