Methanol → 1-(4-Benzyl-morpholin-2-yl)-1-(2-methoxy-benzyl)-2-(2-methoxy-phenyl)-ethylamine diacetate

HRID 30332Notes

Reaction equation

HRID 30332 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]#[N:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:16][O:17][C:18]1[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=1[CH2:20][Mg]Cl.CO.[CH2:29]([O:31][CH2:32][CH3:33])C>>[C:10]([OH:17])(=[O:11])[CH3:14].[C:18]([OH:17])(=[O:31])[CH3:26].[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]([NH2:15])([CH2:6][C:7]2[CH:2]=[CH:3][CH:4]=[CH:33][C:32]=2[O:31][CH3:29])[CH2:20][C:19]2[CH:23]=[CH:24][CH:25]=[CH:26][C:18]=2[O:17][CH3:16])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 887MethanolHCID 3283Diethyl EtherHCID 156511954-Benzylmorpholine-2-carbonitrileHCID 178489472HCID 178489472, compound

Product 1

HCID 866118321-(4-Benzyl-morpholin-2-yl)-1-(2-methoxy-benzyl)-2-(2-methoxy-phenyl)-ethylamine diacetate

Conditions

Temperature
-10 °C

Procedure

To a solution of 4-benzyl-morpholine-2-carbonitrile (10 g, 49.5 mmol) in dry diethyl ether (100 mL) at −10° C. under an atmosphere of nitrogen is added a solution of 2-methoxybenzylmagnesium chloride (0.25M solution in tetrahydrofuran, 218 mL, 54.5 mmol) available from Aldrich Chemical Company or Rieke Metals) and the reaction mixture is further stirred at −10° C. for 30 minutes. Then the reaction is allowed to warm to room temperature and stirred overnight The reaction is then cooled to 0° C. and quenched by addition of hydrochloric acid (5N aqueous solution, 50 mL) and the resulting mixture is stirred for 10 minutes at 0° C. Next the solution is basified with sodium hydroxide (2N aqueous solution), filtered through Celite® then extracted with diethyl ether, the organics collected, dried (MgSO4) and the solvent removed under reduced pressure to give a residue which is taken up into methanol and purified by SCX-2 chromatography prior to silica gel chromatography (eluent, ethyl acetate/n-hexane, 0/100 to 40/60 [v/v]). The fractions containing the correct mass (FIA+[M+H]+=447) are collected and purified via preparative HPLC to give 80 (72 mg). MW 566.69; C28H34N2O3.C4H8O4; LCMS (12 minutes method): m/z)=447.2 [M−C4H8O4+H]+ RT 4.60 min.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred overnight The reaction
  3. temperatureis then cooled to 0° C.
  4. customquenched by addition of hydrochloric acid (5N aqueous solution, 50 mL)
  5. stirringthe resulting mixture is stirred for 10 minutes at 0° C
  6. filtrationfiltered through Celite®
  7. extractionthen extracted with diethyl ether
  8. dry with materialthe organics collected, dried (MgSO4)
  9. customthe solvent removed under reduced pressure
  10. customto give a residue which
  11. custompurified by SCX-2 chromatography
  12. additionThe fractions containing the correct mass (FIA+[M+H]+=447)
  13. customare collected
  14. custompurified via preparative HPLC

Sources & evidence

ORD record
ord-765a2e5e84114950ba107bd0dea2d774
Source dataset
uspto-grants-2008_09
Patent number
US07423037B2

Reaction notes

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