1(2H)-Naphthalenone, 3,4-dihydro-2-((dimethylamino)methyl)- → alpha-(2-dimethylaminomethyl-1,2,3,4-tetrahydro-1-hydroxy-1-naphthyl)-N-methyl-o-toluamide

HRID 1076292Notes

Reaction equation

HRID 1076292 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([NH:6][CH3:7])=[O:5].C([Li])CCC.[CH3:17][N:18]([CH2:20][CH:21]1[CH2:30][CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22]1=[O:31])[CH3:19].[Cl-].[NH4+]>CCCCCC.O1CCCC1>[CH3:19][N:18]([CH2:20][CH:21]1[CH2:30][CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22]1([CH2:1][C:2]1[C:3]([C:4]([NH:6][CH3:7])=[O:5])=[CH:8][CH:9]=[CH:10][CH:11]=1)[OH:31])[CH3:17]

Participants

7

Reactant 4

HCID 238121(2H)-Naphthalenone, 3,4-dihydro-2-((dimethylamino)methyl)-HCID 25517Ammonium ChlorideHCID 75111N-methyl-2-toluamideHCID 178418339Butyllithium

Product 1

HCID 21540120alpha-(2-dimethylaminomethyl-1,2,3,4-tetrahydro-1-hydroxy-1-naphthyl)-N-methyl-o-toluamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
5 °C

Procedure

To a flask equipped with a stirrer, dropping funnel, condenser and gas inlet tube maintained under a nitrogen atmosphere there is added at room temperature 40.0 g (0.28 mole) of o-methyl-N-methyl benzamide and 250 ml. of anhydrous tetrahydrofuran. The reaction flask is immersed in an ice bath and cooled to an internal temperature of 5°C. Stirring is initiated and 380 ml. of 1.6 m. n-butyllithium (0.616 mole) in hexane is added dropwise in ca. 1 hour maintaining the temperature below 8°C. The resulting red dilithio salt is stirred at 5°C. for 1 additional hour and the reaction flask is then immersed in a dry-ice acetone bath and cooled to an internal temperature of -60°C. To the cold reaction mixture a solution of 56.8 g. (0.28 mole) of 2-(dimethylaminomethyl)-3,4-dihydro-1-(2H)-naphthalenone in 140 ml. of anhydrous tetrahydrofuran is added dropwise in ca. 45 min. maintaining the temperature between -60°C and -50° C. The resulting reaction mixture is stirred at -60°C. for 1 hour, allowed to warm to 0°C in ca 1 hour, and then treated with 200 ml. of saturated aqueous ammonium chloride while maintaining the temperature below 10°C. The resulting two layers are separated and the tetrahydrofuran layer is dried over magnesium sulfate, filtered and evaporated. The residue is chromatographed on silica gel with benzene; ethylacetate (1:1) to provide α-(2-dimethylaminomethyl-1,2,3,4-tetrahydro-1-hydroxy-1-naphthyl)-N-methyl-o-toluamide.

Workup

  1. customTo a flask equipped with a stirrer
  2. temperaturemaintained under a nitrogen atmosphere
  3. customThe reaction flask is immersed in an ice bath
  4. temperaturemaintaining the temperature below 8°C
  5. customthe reaction flask is then immersed in a dry-ice acetone bath
  6. temperaturecooled to an internal temperature of -60°C
  7. customTo the cold reaction mixture a solution of 56.8 g
  8. temperaturemaintaining the temperature between -60°C and -50° C
  9. customThe resulting reaction mixture
  10. stirringis stirred at -60°C. for 1 hour
  11. temperatureto warm to 0°C in ca 1 hour
  12. additiontreated with 200 ml
  13. customThe resulting two layers are separated
  14. dry with materialthe tetrahydrofuran layer is dried over magnesium sulfate
  15. filtrationfiltered
  16. customevaporated
  17. customThe residue is chromatographed on silica gel with benzene

Sources & evidence

ORD record
ord-1a31488283da4c669965a7c2c7da03fe
Source dataset
uspto-grants-1976_05
Patent number
US03956391

Reaction notes

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