Trifluoroacetic acid → HCID 69635392, compound

HRID 856236Notes

Reaction equation

HRID 856236 reaction equation
[CH3:1][N:2]([CH2:18][C@:19]1([CH3:30])[O:23][C:22]2=[N:24][C:25]([N+:27]([O-:29])=[O:28])=[CH:26][N:21]2[CH2:20]1)[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13]C(C)(C)C)=[O:12])[CH2:7][CH2:6]1.FC(F)(F)C(O)=O.[F:38][C:39]([F:49])([F:48])[C:40]1[CH:47]=[CH:46][C:43]([CH2:44]O)=[CH:42][CH:41]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>C(Cl)Cl.CN(C=O)C.O>[CH3:1][N:2]([CH2:18][C@:19]1([CH3:30])[O:23][C:22]2=[N:24][C:25]([N+:27]([O-:29])=[O:28])=[CH:26][N:21]2[CH2:20]1)[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][CH2:44][C:43]2[CH:42]=[CH:41][C:40]([C:39]([F:38])([F:48])[F:49])=[CH:47][CH:46]=2)=[O:12])[CH2:7][CH2:6]1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 676844-(Trifluoromethyl)benzenemethanolHCID 682631,1'-CarbonyldiimidazoleHCID 69635278HCID 69635278, compound

Product 1

HCID 69635392HCID 69635392, compoundYield 53%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Tert-butyl (S)-4-[2-(N-methyl-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethylamino)-ethyl]piperazine-1-carboxylate prepared in Example 173 (300 mg, 0.71 mmol) was dissolved in methylene chloride (5 ml). To the solution, trifluoroacetic acid (5 ml) was added followed by stirring at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure and added methylene chloride (2 ml) and triethylamine (2 ml). After stirring for 5 minutes at room temperature, the solution was concentrated under reduced pressure. The residue was dissolved in DMF (15 ml). To the solution, a mixture of 4-trifluoromethylbenzyl alcohol (373 mg, 2.12 mmol) and 1,1′-carbonyldiimidazole (344 mg, 2.12 mmol) in DMF (5 ml) stirred at room temperature for 3 hours was added followed by stirring at room temperature for 1 hour. The reaction mixture was poured into water and extracted with ethyl acetate. The organic phase was washed with a saturated saline solution and dried over magnesium sulfate. After filtration, the resulting filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/methanol=50/1) and crystallized from methylene chloride-isopropyl ether to afford 4-trifluoromethylbenzyl (S)-4-[2-(N-methyl-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethylamino)ethyl]piperazine-1-carboxylate (196 mg, yield 53%) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionadded methylene chloride (2 ml) and triethylamine (2 ml)
  3. stirringAfter stirring for 5 minutes at room temperature
  4. concentrationthe solution was concentrated under reduced pressure
  5. dissolutionThe residue was dissolved in DMF (15 ml)
  6. stirringstirred at room temperature for 3 hours
  7. additionwas added
  8. stirringby stirring at room temperature for 1 hour
  9. extractionextracted with ethyl acetate
  10. washThe organic phase was washed with a saturated saline solution
  11. dry with materialdried over magnesium sulfate
  12. filtrationAfter filtration
  13. concentrationthe resulting filtrate was concentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=50/1)
  15. customcrystallized from methylene chloride-isopropyl ether

Sources & evidence

ORD record
ord-4daa70dd40654a119f54524806070bd0
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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