Triethylamine → (3S,5R)-5-[(1S,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-3-methylmorpholin-2-one

HRID 20413Notes

Reaction equation

HRID 20413 reaction equation
[CH3:1][O:2][C:3](=[O:14])[C@H:4](OS(C(F)(F)F)(=O)=O)[CH3:5].Cl.Cl.[NH2:17][C@@H:18]([C@H:21]([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)[C@@H:22]([N:32]([CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([F:31])[CH:25]=1)CO.C(N(CC)CC)C>ClCCl>[CH2:48]([O:47][C@@H:21]([C@@H:18]1[NH:17][C@@H:4]([CH3:5])[C:3](=[O:14])[O:2][CH2:1]1)[C@@H:22]([N:32]([CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH2:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([F:31])[CH:25]=1)[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11064395Propanoic acid, 2-[[(trifluoromethyl)sulfonyl]oxy]-, methyl ester, (2R)-HCID 68561220HCID 68561220, compound

Product 1

HCID 68563893(3S,5R)-5-[(1S,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-3-methylmorpholin-2-oneYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Add 2(R)-trifluoromethanesulfonyloxypropionic acid methyl ester (6 g, 25.42 mmol) to a solution of (2R,3S,4S)-2-amino-3-benzyloxy-4-dibenzylamino-5-(3,5-difluorophenyl)-pentan-1-ol bishydrochloride (4.7 g, 7.94 mmol) and triethylamine (5 mL, 35.87 mmol) in dichloromethane (150 mL). Stir the reaction mixture at room temperature for 68-hours. Dilute with dichloromethane and wash with 5% aqueous citric acid, saturated aqueous sodium chloride, dry (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 10:90 to 20:80 ethyl acetate:hexanes) to give the desired compound (2.93 g, 65%).

Workup

  1. washwash with 5% aqueous citric acid, saturated aqueous sodium chloride
  2. dry with materialdry (magnesium sulfate)
  3. filtrationfilter
  4. concentrationconcentrate
  5. custompurify
  6. wash(silica gel chromatography, eluting with 10:90 to 20:80 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-97bebf59ffe54f3487eaedd4e21399b2
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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