L-Methionine → (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methoxypropyl)-phenol

HRID 1631842Notes

Reaction equation

HRID 1631842 reaction equation
Cl.C[O:3][C:4]1[CH:5]=[C:6]([C@H:10]([CH2:17][CH3:18])[C@@H:11](C)[CH2:12][N:13]([CH3:15])[CH3:14])[CH:7]=[CH:8][CH:9]=1.N[C@H]([C:25](O)=[O:26])CCSC>CS(O)(=O)=O>[CH3:14][N:13]([CH3:15])[CH2:12][C@H:11]([O:26][CH3:25])[C@@H:10]([C:6]1[CH:5]=[C:4]([OH:3])[CH:9]=[CH:8][CH:7]=1)[CH2:17][CH3:18]

Participants

4

Reactant 2

HCID 6137L-MethionineHCID 247860813(3-Methoxyphenyl)-N,N,2-trimethyl pentane-1-amine hydrochloride, (2R,3R)-

Product 1

HCID 86690044(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methoxypropyl)-phenolYield 105.3%

Reagents, catalysts & solvents 1

HCID 6395Methanesulfonic AcidSolvent

Conditions

Temperature
77.5 °C

Procedure

In 28 mL of methanesulfonic acid, (2R,3R)-3-(3-methoxyphenyl)-N,N,2-trimethylpentan-1-amine HCl (6.0 g, 0.022 moles) is dissolved, and methionine (4.7 g, 0.031 moles) is added to the solution. The reaction is stirred at the temperature of 75-80° C. for 16-20 hours. It is then cooled to 15-25° C. and the following is added: purified water (20 mL), slowly at this temperature. The pH is brought to the value of 10-11 by means of the addition of 28% NaOH (about 35 mL), maintaining the temperature below 50° C. Then, ethyl acetate (30 mL) is added to the mixture. The mixture is then stirred for 30 minutes and the organic phase is separated. The organic phase, with dark color, is filtered over a silica panel and washed with 30 mL of ethyl acetate. A yellowish transparent solution is obtained. The solvent is removed under vacuum, obtaining about 5.5 g of oil which, left at ambient temperature, solidifies.

Workup

  1. temperatureIt is then cooled to 15-25° C.
  2. additionthe following is added
  3. custompurified water (20 mL)
  4. additionThe pH is brought to the value of 10-11 by means of the addition of 28% NaOH (about 35 mL)
  5. temperaturemaintaining the temperature below 50° C
  6. additionThen, ethyl acetate (30 mL) is added to the mixture
  7. stirringThe mixture is then stirred for 30 minutes
  8. customthe organic phase is separated
  9. filtrationThe organic phase, with dark color, is filtered over a silica panel
  10. washwashed with 30 mL of ethyl acetate
  11. customA yellowish transparent solution is obtained
  12. customThe solvent is removed under vacuum

Sources & evidence

ORD record
ord-6512ab6cb2264bd6bd1fe08786a0ec29
Source dataset
uspto-grants-2014_07
Patent number
US08791287B2

Reaction notes

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