Trifluoroacetic acid → HCID 69479932, compound

HRID 856244Notes

Reaction equation

HRID 856244 reaction equation
C([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([NH:27][CH3:28])[C@@:15]2([CH3:26])[O:19][C:18]3=[N:20][C:21]([N+:23]([O-:25])=[O:24])=[CH:22][N:17]3[CH2:16]2)[CH2:10][CH2:9]1)=[O:7])(C)(C)C.FC(F)(F)C(O)=O.[F:36][C:37]([F:47])([F:46])[C:38]1[CH:45]=[CH:44][C:41]([CH2:42]O)=[CH:40][CH:39]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>C(Cl)Cl.CN(C=O)C.O>[F:36][C:37]([F:46])([F:47])[C:38]1[CH:45]=[CH:44][C:41]([CH2:42][O:5][C:6]([N:8]2[CH2:13][CH2:12][CH:11]([CH:14]([NH:27][CH3:28])[C@@:15]3([CH3:26])[O:19][C:18]4=[N:20][C:21]([N+:23]([O-:25])=[O:24])=[CH:22][N:17]4[CH2:16]3)[CH2:10][CH2:9]2)=[O:7])=[CH:40][CH:39]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 676844-(Trifluoromethyl)benzenemethanolHCID 682631,1'-CarbonyldiimidazoleHCID 69481758HCID 69481758, compound

Product 1

HCID 69479932HCID 69479932, compoundYield 68%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

(S)-2-{[1-(Tert-butoxycarbonyl)piperidin-4-yl]-N-methylaminomethyl}-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole prepared in Example 225 (400 mg, 1.01 mmol) was dissolved in methylene chloride (1 ml). To the solution, trifluoroacetic acid (1 ml) was added followed by stirring at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure and added methylene (1 ml) chloride and triethylamine (2 ml). The solution was stirred at room temperature for 5 minutes and then concentrated under reduced pressure, and the residue was dissolved in DMF (8 ml). To the solution, a mixture of 4-(trifluoromethyl)benzyl alcohol (267 mg, 1.51 mmol) and 1,1′-carbonyldiimidazole (246 mg, 1.51 mmol) in DMF (2 ml) stirred at room temperature for 4 hours was added followed by stirring at room temperature overnight. The reaction mixture was poured into water and extracted with ethyl acetate. The organic phase was washed with a saturated saline solution, dried over magnesium sulfate and then filtered. The resulting filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1) and crystallized from methylene chloride-isopropyl ether to afford (S)-2-{[l-(4-trifluoromethylbenzyloxycarbonyl)piperidin-4-yl]-N-methylaminomethyl}-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole (341 mg, yield 68%) as a light yellow powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionadded methylene (1 ml) chloride and triethylamine (2 ml)
  3. stirringThe solution was stirred at room temperature for 5 minutes
  4. concentrationconcentrated under reduced pressure
  5. dissolutionthe residue was dissolved in DMF (8 ml)
  6. stirringstirred at room temperature for 4 hours
  7. additionwas added
  8. stirringby stirring at room temperature overnight
  9. extractionextracted with ethyl acetate
  10. washThe organic phase was washed with a saturated saline solution
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationThe resulting filtrate was concentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1)
  15. customcrystallized from methylene chloride-isopropyl ether

Sources & evidence

ORD record
ord-080fc86f663746afa6f6360fe2496134
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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