N'-Hydroxybenzenecarboximidamide → HCID 46956711, compound

HRID 218323

Reaction equation

HRID 218323 reaction equation
Cl.[CH2:2]([N:9]1[CH2:14][CH2:13][O:12][CH:11]([C:15]([OH:17])=O)[CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=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.O[N:61]=[C:62]([NH2:69])[C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1>CN(C)C=O.O>[CH2:2]([N:9]1[CH2:14][CH2:13][O:12][CH:11]([C:15]2[O:17][N:69]=[C:62]([C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)[N:61]=2)[CH2:10]1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

8

Reactant 5

HCID 69186N'-HydroxybenzenecarboximidamideHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27763524-Benzylmorpholine-2-carboxylic acid hydrochloride2×HCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 46956711HCID 46956711, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-benzyl-2-morpholinecarboxylic acid hydrochloride (intermediate 20, 1.5 g, 5.82 mmol) in N,N-dimethylformamide (10 ml) was added 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluroniumtetrafluoroborate (2.2 g, 6.98 mmol), 1-hydroxybenzotriazole hydrate (236 mg, 1.74 mmol) and N,N-diisopropylethylamine (5.1 ml, 29.1 mmol), and the reaction mixture was stirred at room temperature for 30 minutes. After the addition of N′-hydroxybenzamidine (792 mg, 5.82 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 the 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; 25% ethyl acetate in hexane) to afford 4-benzyl-2-(3-phenyl-1,2,4-oxadiazol-5-yl)morpholine (intermediate 21, 1.44 g, 77%) 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; 25% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-7841db3106c34e3c9282b61dd83d6901
Source dataset
uspto-grants-2012_06
Patent number
US08198437B2

Linked notes

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