Benzoic Acid → 4-Benzyl-2-(5-phenyl-1,2,4-oxadiazol-3-yl)morpholine

HRID 218327Notes

Reaction equation

HRID 218327 reaction equation
[C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[CH2:52]([N:59]1[CH2:64][CH2:63][O:62][CH:61]([C:65]([NH2:68])=[N:66]O)[CH2:60]1)[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1>CN(C)C=O.O>[CH2:52]([N:59]1[CH2:64][CH2:63][O:62][CH:61]([C:65]2[N:68]=[C:1]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[O:9][N:66]=2)[CH2:60]1)[C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1

Participants

8

Reactant 5

HCID 243Benzoic AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27960291-Hydroxybenzotriazole hydrateHCID 748942584-Benzyl-N-hydroxymorpholine-2-carboximidamide2×

Product 1

HCID 580978824-Benzyl-2-(5-phenyl-1,2,4-oxadiazol-3-yl)morpholineYield 75%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of benzoic acid (2.30 g, 19.1 mmol) in N,N-dimethylformamide (20 ml) was added 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluroniumtetrafluoroborate (6.15 g, 19.1 mmol), 1-hydroxybenzotriazole hydrate (518 mg, 3.83 mmol) and N,N-diisopropylethylamine (11.0 ml, 63.8 mmol), and the reaction mixture was stirred at room temperature for 30 minutes. After addition of 4-benzyl-N′-hydroxymorpholine-2-carboxamidine (intermediate 26, 3.0 g, 12.8 mmol), the reaction mixture was stirred at room temperature for one hour, and then heated to 110° C. When the reaction was complete (checked by thin layer chromatography), excess reagent was decomposed by addition of water and the aqueous layer was extracted with ethyl acetate. The extract was washed with water and brine, dried over magnesium sulfate, and concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel (eluent: 30% ethyl acetate in hexane) to afford 4-benzyl-2-(5-phenyl-1,2,4-oxadiazol-3-yl)morpholine (intermediate 27, 3.08 g, 75%) as a colorless oil.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for one hour
  2. temperatureheated to 110° C
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washThe extract was washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography on silica gel (eluent: 30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-efe61ac0ab2743c7a9464d5ce4b078d4
Source dataset
uspto-grants-2012_06
Patent number
US08198437B2

Reaction notes

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