Sulfuric Acid → 3(3-Methoxyphenyl)-N,N,2-trimethyl pentane-1-amine, (2R,3R)-

HRID 534701Notes

Reaction equation

HRID 534701 reaction equation
[CH3:1][N:2]([CH3:18])[CH2:3][C@H:4]([CH3:17])[C@:5]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[CH:10]=1)(O)[CH2:6][CH3:7].S(=O)(=O)(O)O.CS(O)(=O)=O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O.C1CCCCC1.O1CCCC1>[CH3:16][O:15][C:11]1[CH:10]=[C:9]([C@H:5]([CH2:6][CH3:7])[C@@H:4]([CH3:17])[CH2:3][N:2]([CH3:18])[CH3:1])[CH:14]=[CH:13][CH:12]=1

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 6101p-Toluenesulfonic acidHCID 6395Methanesulfonic AcidHCID 9942979(alphaR)-alpha-[(1S)-2-(Dimethylamino)-1-methylethyl]-alpha-ethyl-3-methoxybenzenemethanol

Product 1

HCID 112533283(3-Methoxyphenyl)-N,N,2-trimethyl pentane-1-amine, (2R,3R)-

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8078CyclohexaneSolvent

Conditions

Temperature
20 °C

Procedure

Accordingly the compound (2S,3R)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methyl pentan-3-ol of Formula-V was charged in the solvent tetrahydrofuran and under stirring charged concentrated sulfuric acid at temperature of 20-30° C. The reaction mixture is stirred and charged methanesulfonic acid or para toluenesulfonic acid and solvent cyclohexane. Stirred and raised the temperature to reflux. Maintained the reaction mass at reflux temperature for 3-5 hours with simultaneous removal of water. Cooled the reaction mass to 20° C. and separated the organic layer. Charged the organic layer in an autoclave and diluted the layer with tetrahydrofuran. Charged the catalyst Pd/C. Purged the autoclave with nitrogen gas and followed with hydrogen gas pressure of 5-7 kg. Maintained the reaction mass at 25-30° C. for 2-4 hours. After completion of the reaction the reaction mass was filtered and the filtrate was concentrated under reduced pressure to get the residual mass. Diluted the residual mass with water and extracted with toluene. Separated the aqueous layer and adjusted the pH to 9-10 with aqueous solution of sodium hydroxide. Extracted the aqueous layer with diisopropyl ether, separated the organic layer and concentrated under reduced pressure below 40° C. to get the compound (2R,3R)-3-(3-methoxyphenyl)-N,N,2-trimethylpentan-1-amine of Formula-VII.

Workup

  1. stirringThe reaction mixture is stirred
  2. stirringStirred
  3. temperatureraised the temperature
  4. temperatureto reflux
  5. temperatureMaintained the reaction mass
  6. temperatureat reflux temperature for 3-5 hours
  7. customwith simultaneous removal of water
  8. customseparated the organic layer
  9. additionCharged the organic layer in an autoclave
  10. additiondiluted the layer with tetrahydrofuran
  11. additionCharged the catalyst Pd/C
  12. customPurged the autoclave with nitrogen gas
  13. temperatureMaintained the reaction mass at 25-30° C. for 2-4 hours
  14. customAfter completion of the reaction the reaction mass
  15. filtrationwas filtered
  16. concentrationthe filtrate was concentrated under reduced pressure
  17. customto get the residual mass
  18. extractionextracted with toluene
  19. customSeparated the aqueous layer
  20. extractionExtracted the aqueous layer with diisopropyl ether
  21. customseparated the organic layer
  22. concentrationconcentrated under reduced pressure below 40° C.

Sources & evidence

ORD record
ord-ec34da577e9e48c2aa61af09ac3e4443
Source dataset
uspto-grants-2014_10
Patent number
US08853456B2

Reaction notes

Loading…