Carbon Dioxide → 4,4-Dimethylcyclohexyl-N-methyl-[2,1,3]-benzoxadiazole-5-carboxamide

HRID 238536Notes

Reaction equation

HRID 238536 reaction equation
[CH3:1][NH2:2].Cl.CN.[OH-].[Na+].C(=O)=O.[CH3:11][C:12]1([CH3:19])[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]1.[N:20]1[O:21][N:22]=[C:23]2[CH:28]=[C:27]([C:29](Cl)=[O:30])[CH:26]=[CH:25][C:24]=12>CO.C1COCC1.C(Cl)(Cl)Cl.[Pd]>[CH3:11][C:12]1([CH3:19])[CH2:17][CH2:16][CH:15]([C:28]2[C:23]3[C:24](=[N:20][O:21][N:22]=3)[CH:25]=[CH:26][C:27]=2[C:29]([NH:2][CH3:1])=[O:30])[CH2:14][CH2:13]1

Participants

11

Reactant 6

HCID 280Carbon DioxideHCID 6329MethylamineHCID 14798Sodium HydroxideHCID 138166Cyclohexanone, 4,4-dimethyl-HCID 27354532,1,3-Benzoxadiazole-5-carbonyl chlorideHCID 6364545Methylamine hydrochloride

Product 1

HCID 866415484,4-Dimethylcyclohexyl-N-methyl-[2,1,3]-benzoxadiazole-5-carboxamide

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methylamine, generated by heating a mixture of methylamine hydrochloride (10 g) and sodium hydroxide pellets (18 g), was condensed (dry ice trap) into a solution of 4,4-dimethylcyclohexanone (1.0 g, 7.9 mmol) in 40 ml of methanol and 20 ml of THF. 10% Pd on C (400 mg) was added and the mix was hydrogenated at room temperature over night. The solids were filtered off, and the mixture concentrated under vacuum. This material and triethylamine (2 ml) were dissolved in chloroform (50 ml) and a solution of [2,1,3]-benzoxadiazole-5-carbonylchloride (900 mg, 4.9 mmol), in chloroform (40 ml), was added slowly at room temperature. After stirring the mixture for 1 hour, the organic phase was washed with 1N HCl and cone. NaHCO3 solution, dried over sodium sulfate, and concentrated under vacuum to yield an oil, which was purified using silica gel chromatography eluting with chloroform/ethyl acetate/hexane (10:20:70), to give a white solid, after crystallization from methyl-t-butyl ether (MTBE)/hexane (38 mg). Mp=143-5° C., 1H NMR (300 MHz, CDCl3, rotamers) δ 7.91 (d, 1H, J=8.7 Hz); 7.81 (sb, 1H); 7.45-7.36 (m, 1H); 4.52-4.35 and 3.45-3.30 (m+m, 1H); 3.04 and 2.89 (s+s, 3H) and 1.95-0.80 ppm (m, 14H).

Workup

  1. temperatureby heating
  2. waitthe mix was hydrogenated at room temperature over night
  3. filtrationThe solids were filtered off
  4. concentrationthe mixture concentrated under vacuum
  5. dissolutionThis material and triethylamine (2 ml) were dissolved in chloroform (50 ml)
  6. washthe organic phase was washed with 1N HCl and cone
  7. dry with materialNaHCO3 solution, dried over sodium sulfate
  8. concentrationconcentrated under vacuum
  9. customto yield an oil, which
  10. customwas purified
  11. washeluting with chloroform/ethyl acetate/hexane (10:20:70)
  12. customto give a white solid
  13. customafter crystallization from methyl-t-butyl ether (MTBE)/hexane (38 mg)

Sources & evidence

ORD record
ord-b589ae8a96cd483eae9768a2a448ea10
Source dataset
uspto-grants-2014_02
Patent number
US08642633B2

Reaction notes

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