2-Chlorobenzoxazole → HCID 9794818, compound

HRID 1815750Notes

Reaction equation

HRID 1815750 reaction equation
Cl[C:2]1[O:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[N:11]12[CH2:19][CH2:18][CH:15]([CH2:16][CH2:17]1)[NH:14][CH2:13][CH2:12]2.CCN(C(C)C)C(C)C>CO.C(Cl)(Cl)Cl.C([O-])(O)=O.[Na+]>[O:3]1[C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=[C:2]1[N:14]1[CH:15]2[CH2:18][CH2:19][N:11]([CH2:17][CH2:16]2)[CH2:12][CH2:13]1

Participants

7

Reactant 3

HCID 119862-ChlorobenzoxazoleHCID 81531DiisopropylethylamineHCID 3984071,4-Diazabicyclo(3.2.2)nonane

Product 1

HCID 9794818HCID 9794818, compoundYield 35%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 516892Sodium BicarbonateSolvent

Procedure

2-Chlorobenzoxazole (Aldrich, 99 μL, 0.87 mmol) was added to a solution of 1,4-diazabicyclo[3.2.2]nonane (100 mg, 0.79 mmol) in methanol (2.65 mL) at 0° C. The reaction mixture was allowed to slowly warm to RT. After a period of 16 h iPr2NEt (138 μL, 0.79 mmol) was added and the mixture was stirred at RT for 4.5 h at which time it was diluted with CHCl3 and NaHCO3. The layers were partitioned and the aqueous layer was extracted with CHCl3 (×3). The combined organic layers were washed with H2O and brine, dried (Na2SO4), filtered and concentrated. The crude residue was purified by chromatography (Biotage, 12L) eluting with 4% MeOH in CHCl3 containing 20 drops of NH4OH per liter of eluent to afford 67 mg (35%) of the title compound as a yellow oil: 1H NMR (CDCl3, 400 MHz) δ 7.30 (d, 1H, J=7.5 Hz), 7.19 (d, 1H, J=7.9 Hz), 7.10 (t, 1H, J=7.5 Hz), 6.94 (t, 1H, J=7.9 Hz), 4.46 (s, 1H), 3.87, (t, 2H, J=5.8 Hz), 3.12-2.92 (m, 6H), 2.15-2.05 (m, 2H), 1.79-1.70 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ 161.8, 148.9, 143.7, 124.1, 120.3, 116.1, 108.7, 57.3, 50.3, 46.5, 44.4, 27.1; MS (Cl) m/z 244.3 (M+1). The hydrochloride salt was prepared by dissolving the title compound in iPrOH and adding 0.1 mL of 6 M hydrochloric acid.

Workup

  1. customThe layers were partitioned
  2. extractionthe aqueous layer was extracted with CHCl3 (×3)
  3. washThe combined organic layers were washed with H2O and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by chromatography (Biotage, 12L)
  8. washeluting with 4% MeOH in CHCl3 containing 20 drops of NH4OH per liter of eluent

Sources & evidence

ORD record
ord-d807c1df559944a3a97178234b663b2e
Source dataset
uspto-grants-2005_04
Patent number
US06881734B2

Reaction notes

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