Triethylamine → N-adamantan-2-yl-2,3-dihydro-4H-1,4-benzoxazine-4-carboxamide

HRID 1515352Notes

Reaction equation

HRID 1515352 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.C(N(CC)CC)C.[O:20]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[NH:23][CH2:22][CH2:21]1.Cl.[CH:31]12[CH2:40][CH:35]3[CH2:36][CH:37]([CH2:39][CH:33]([CH2:34]3)[CH:32]1[NH2:41])[CH2:38]2>C(Cl)(Cl)Cl.O>[CH:31]12[CH2:40][CH:35]3[CH2:36][CH:37]([CH2:39][CH:33]([CH2:34]3)[CH:32]1[NH:41][C:5]([N:23]1[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[O:20][CH2:21][CH2:22]1)=[O:11])[CH2:38]2

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 253312-Aminoadamantane hydrochlorideHCID 94429TriphosgeneHCID 5850963,4-Dihydro-2H-1,4-benzoxazine

Product 1

HCID 25134157N-adamantan-2-yl-2,3-dihydro-4H-1,4-benzoxazine-4-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent2×

Procedure

To a solution of triphosgene (119 mg) in chloroform (3 ml), a solution of triethylamine (332 μl) and 3,4-dihydro-2H-1,4-benzoxazine obtained in Reference Example 14 (108 mg) in chloroform (2 ml) was added under ice cooling and stirred at the same temperature for 10 minutes. To the reaction mixture, 2-adamantaneamine hydrochloride (150 mg) and triethylamine (166 μl) were then added and stirred at room temperature for 16 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed sequentially with 1M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate and brine. After drying over anhydrous magnesium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=4:1). The resulting residue was dissolved in a small volume of chloroform and converted into a powder form by addition of diethyl ether, and then collected by filtration to give the titled compound (Compound 34, 96 mg) as a colorless powder.

Workup

  1. additionwas added under ice cooling
  2. stirringstirred at room temperature for 16 hours
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed sequentially with 1M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate and brine
  5. dry with materialAfter drying over anhydrous magnesium sulfate
  6. filtrationthe desiccant was filtered off
  7. distillationthe solvent was distilled off under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=4:1)
  9. dissolutionThe resulting residue was dissolved in a small volume of chloroform
  10. additionconverted into a powder form by addition of diethyl ether
  11. filtrationcollected by filtration

Sources & evidence

ORD record
ord-657cb08e78184b7e8515e5106133a7c7
Source dataset
uspto-grants-2012_07
Patent number
US08222417B2

Reaction notes

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