Toluene → 4-(5-Phenyl-benzooxazol-2-YL)-1,4-diaza-bicyclo[3.2.2]nonane

HRID 1815757Notes

Reaction equation

HRID 1815757 reaction equation
[N:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[NH:4][CH2:3][CH2:2]2.Cl[C:11]1[O:12][C:13]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:16][C:14]=2[N:15]=1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>C(OCC)(=O)C.O>[C:20]1([C:17]2[CH:18]=[CH:19][C:13]3[O:12][C:11]([N:4]4[CH:5]5[CH2:8][CH2:9][N:1]([CH2:7][CH2:6]5)[CH2:2][CH2:3]4)=[N:15][C:14]=3[CH:16]=2)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 3984071,4-Diazabicyclo(3.2.2)nonaneHCID 141698182-Chloro-5-phenylbenzoxazoleHCID 23676156Sodium t-butoxide

Product 1

HCID 224958074-(5-Phenyl-benzooxazol-2-YL)-1,4-diaza-bicyclo[3.2.2]nonaneYield 42.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

1,4-Diazabicyclo[3.2.2]nonane (504 mg, 4.0 mmol) was added to a mixture of 2-chloro-5-phenylbenzoxazole (919 mg, 4.0 mmol), sodium tert-butoxide (423 mg, 4.4 mmol) and toluene (4 mL) at RT. The mixture was stirred at RT for 16 h and water (10 mL) and ethyl acetate (10 mL) were added. The layers were partitioned and the aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated and the residue was purified by chromatography (Biotage, 40S) eluting with 4% MeOH in CHCl3 with 20 drops of NH4OH per liter of eluent to afford 540 mg (42%) of the title compound as an oil: 1H NMR (CDCl3, 400 MHz) δ 7.60-7.56 (m, 3H), 7.42 (t, 2H, J=7.7 Hz), 7.33-7.20 (m, 3H), 4.51 (s, 1H), 3.92 (t, 2H, J=5.8 Hz), 3.17-2.97 (m, 6H), 2.20-2.07 (m, 2H), 1.84-1.75 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ 162.2, 148.6, 144.3, 141.9, 137.9, 129.0, 127.5, 127.1, 119.8, 114.8, 108.8, 57.3, 50.4, 46.5, 44.4, 27.0; MS (Cl) m/z 320.1 (M+1). The hydrochloride salt was prepared by diluting the title compound in ethyl acetate and adding a 2.5 N HCl in ethyl acetate solution: mp>300° C.

Workup

  1. customThe layers were partitioned
  2. extractionthe aqueous layer was extracted with ethyl acetate (3×10 mL)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe residue was purified by chromatography (Biotage, 40S)
  7. washeluting with 4% MeOH in CHCl3 with 20 drops of NH4OH per liter of eluent

Sources & evidence

ORD record
ord-fea64d301f41465db09ab85ece9336a1
Source dataset
uspto-grants-2005_04
Patent number
US06881734B2

Reaction notes

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