Sulfuric Acid → HCID 46836960, compound

HRID 1642053Notes

Reaction equation

HRID 1642053 reaction equation
C([N:8]1[CH:13]2[CH2:14][O:15][CH2:16][CH:9]1[CH2:10][O:11][CH2:12]2)C1C=CC=CC=1.C1COCC1.[N:22]1[O:23][N:24]=[C:25]2[CH:30]=[C:29]([C:31](Cl)=[O:32])[CH:28]=[CH:27][C:26]=12.OS(O)(=O)=O>CO.C(O)=O.ClCCl.[Pd].O.C(N(CC)CC)C>[N:22]1[O:23][N:24]=[C:25]2[CH:30]=[C:29]([C:31]([N:8]3[CH:13]4[CH2:14][O:15][CH2:16][CH:9]3[CH2:10][O:11][CH2:12]4)=[O:32])[CH:28]=[CH:27][C:26]=12

Participants

11

Reactant 4

HCID 1118Sulfuric AcidHCID 8028TetrahydrofuranHCID 27354532,1,3-Benzoxadiazole-5-carbonyl chlorideHCID 11708349HCID 11708349, compound

Product 1

HCID 46836960HCID 46836960, compound

Reagents, catalysts & solvents 6

HCID 23938PalladiumCatalystHCID 284Formic AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

9-Benzyl-3,7-dioxa-9-azabicyclo-(3.3.1)nonane (650 mg, 2.96 mmol, see: JOC, Vol. 71, No. 1, 2006, 413-415) was dissolved in methanol (20 ml) and formic acid (4 ml). 10% Pd/C (0.3 g) was added and the mixture was hydrogenated over night. The solids were filtered off, and the solvent evaporated. The residue was dissolved in methanol (20 ml) and a solution of HCl in dioxane (2 ml, 4N) was added and the solvent evaporated. The residue was dissolved in dichloromethane (80 ml), THF (20 ml) and triethylamine (3 ml) and a solution of [2,1,3]-benzoxadiazole-5-carbonylchloride (1.0 g, 5.5 mmol) in dichloromethane (10 ml) was added. After stirring the mixture for 0.5 h, water (100 ml) and H2SO4 (→pH2) were added and the organic phase extracted with sodium bicarbonate solution (100 ml), the aqueous was re-extracted with dichloromethane (50 ml) and the combined organics were dried over magnesium sulfate, and concentrated under vacuum. The crude product was purified by silica gel chromatography eluting with hexane/THF (50/50). The product was crystallized from dichloromethane/ethanol, which gave the title compound as an off white solid (590 mg): mp=197-199° C., LC-MS, MH+=276.2; 1H NMR (300 MHz, CDCl3) δ 7.98 (dd, 2H, J=9.0 and 1.2 Hz); 7.94 (t, 1H, J=1.2 Hz); 7.50 (dd, 1H, J=9.0 and 1.2 Hz); 4.52 (s, 2H); 4.21 (d, 2H, J=11.4 Hz); 4.09-4.02 (m, 4H); 3.90 (dd, 2H, J=10.8 and 2.4 Hz); 3.61 ppm (s, 2H).

Workup

  1. waitthe mixture was hydrogenated over night
  2. filtrationThe solids were filtered off
  3. customthe solvent evaporated
  4. dissolutionThe residue was dissolved in methanol (20 ml)
  5. additiona solution of HCl in dioxane (2 ml, 4N) was added
  6. customthe solvent evaporated
  7. dissolutionThe residue was dissolved in dichloromethane (80 ml)
  8. extractionthe organic phase extracted with sodium bicarbonate solution (100 ml)
  9. extractionthe aqueous was re-extracted with dichloromethane (50 ml)
  10. dry with materialthe combined organics were dried over magnesium sulfate
  11. concentrationconcentrated under vacuum
  12. customThe crude product was purified by silica gel chromatography
  13. washeluting with hexane/THF (50/50)
  14. customThe product was crystallized from dichloromethane/ethanol, which

Sources & evidence

ORD record
ord-b2df64b79dec4143856133606b9dd1bf
Source dataset
uspto-grants-2012_02
Patent number
US08119632B2

Reaction notes

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