Sulfuric Acid → HCID 46836962, compound

HRID 1642052Notes

Reaction equation

HRID 1642052 reaction equation
C([N:8]1[CH:13]2[CH2:14][CH2:15][CH2:16][CH:9]1[CH2:10][O:11][CH2:12]2)C1C=CC=CC=1.C(N(CC)CC)C.[N:24]1[O:25][N:26]=[C:27]2[CH:32]=[C:31]([C:33](Cl)=[O:34])[CH:30]=[CH:29][C:28]=12.OS(O)(=O)=O>C(O)C.ClCCl.[Pd].O>[N:24]1[O:25][N:26]=[C:27]2[CH:32]=[C:31]([C:33]([N:8]3[CH:13]4[CH2:14][CH2:15][CH2:16][CH:9]3[CH2:10][O:11][CH2:12]4)=[O:34])[CH:30]=[CH:29][C:28]=12

Participants

9

Reactant 4

HCID 1118Sulfuric AcidHCID 8471TriethylamineHCID 27354532,1,3-Benzoxadiazole-5-carbonyl chlorideHCID 12069236HCID 12069236, compound

Product 1

HCID 46836962HCID 46836962, compoundYield 83%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

9-Benzyl-3-oxa-9-azabicyclo-(3.3.1)nonane (3.0 g, 13.8 mmol, see: WO 03004503) was dissolved in ethanol (100 ml), and 10% Pd/C (0.56 g) was added. The mixture was hydrogenated at 100 psi over night. The solids were filtered off, a solution of HCl in dioxane (4 ml, 4N) was added and the solvent evaporated. The residue was dissolved in dichloromethane (100 ml) and triethylamine (8 ml) and a solution of [2,1,3]-benzoxadiazole-5-carbonylchloride (3.5 g, 19.2 mmol) in dichloromethane (10 ml) was added. After stirring the mixture for 20 minutes, water (100 ml) and H2SO4 (→pH2) were added and the organic phase washed with sodium bicarbonate solution (100 ml), the aqueous was re-extracted with dichloromethane (100 ml) and the combined organic phase was dried over magnesium sulfate, and concentrated under vacuum. The crude material was purified by silica gel chromatography eluting with hexane/THF (70/30). The product crystallized, when the solvent is was evaporated slowly, which yielded the title compound as a white solid (3.13 g): mp=128-130° C., LC-MS, MH+=274.2; 1H NMR (300 MHz, CDCl3) δ 7.94 (dd, 2H, J=9.0 and 1.2 Hz); 7.89 (t, 1H, J=1.2 Hz); 7.47 (dd, 1H, J=9.0 and 1.2 Hz); 4.62 (s, 1H); 4.05 (d, 1H, J=11.7 Hz); 3.95-3.89 (m, 2H); 3.79 (d, 1H, J=11.7 Hz); 3.66 (s, 1H); 2.71-2.54 (m, 1H); 2.14-1.69 ppm (m, 5H).

Workup

  1. waitThe mixture was hydrogenated at 100 psi over night
  2. filtrationThe solids were filtered off
  3. additiona solution of HCl in dioxane (4 ml, 4N) was added
  4. customthe solvent evaporated
  5. dissolutionThe residue was dissolved in dichloromethane (100 ml)
  6. washthe organic phase washed with sodium bicarbonate solution (100 ml)
  7. extractionthe aqueous was re-extracted with dichloromethane (100 ml)
  8. dry with materialthe combined organic phase was dried over magnesium sulfate
  9. concentrationconcentrated under vacuum
  10. customThe crude material was purified by silica gel chromatography
  11. washeluting with hexane/THF (70/30)
  12. customThe product crystallized
  13. customwhen the solvent is was evaporated slowly

Sources & evidence

ORD record
ord-568235487c8448c6bd9ddd92c2061a1a
Source dataset
uspto-grants-2012_02
Patent number
US08119632B2

Reaction notes

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