Trifluoroacetic acid → HCID 86760533, compound

HRID 856275Notes

Reaction equation

HRID 856275 reaction equation
[CH3:1][C@@:2]1([CH2:13][N:14]2[CH2:19][CH2:18][CH:17]([NH:20][C:21](=[O:27])[O:22]C(C)(C)C)[CH2:16][CH2:15]2)[O:6][C:5]2=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]2[CH2:3]1.FC(F)(F)C(O)=O.[F:35][C:36]([F:46])([F:45])[C:37]1[CH:44]=[CH:43][C:40]([CH2:41]O)=[CH:39][CH:38]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>C(Cl)Cl.CN(C=O)C.O>[CH3:1][C@@:2]1([CH2:13][N:14]2[CH2:15][CH2:16][CH:17]([NH:20][C:21](=[O:27])[O:22][CH2:41][C:40]3[CH:39]=[CH:38][C:37]([C:36]([F:35])([F:45])[F:46])=[CH:44][CH:43]=3)[CH2:18][CH2:19]2)[O:6][C:5]2=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]2[CH2:3]1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 676844-(Trifluoromethyl)benzenemethanolHCID 682631,1'-CarbonyldiimidazoleHCID 131726573HCID 131726573, compound

Product 1

HCID 86760533HCID 86760533, compoundYield 28.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Tert-butyl (S)-[1-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperidin-4-yl]carbamate prepared in Example 283 (0.300 g, 0.787 mmol) was dissolved in methylene chloride (4 ml). To the solution, trifluoroacetic acid (2 ml) was added followed by stirring at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and added methylene chloride (4 ml) and triethylamine (4 ml). The mixture was stirred at room temperature for 5 minutes and concentrated under reduced pressure. The residue was dissolved in DMF (6 ml). To the solution, a mixture of 4-(trifluoromethyl)benzyl alcohol (0.166 g, 0.944 mmol) in DMF (4 ml) and 1,1′-carbonyldiimidazole (0.153 g, 0.944 mmol) stirred at room temperature for 4 hours was added followed by stirring at room temperature overnight and then at 65° C. for 8 hours. To the reaction mixture, water was added, and the solution was extracted with ethyl acetate twice. The organic phases were combined, washed with water and a saturated saline solution, dried over sodium sulfate and then filtered. The resulting filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/acetone=2/1) and recrystallized from ethyl acetate to afford 4-trifluoromethylbenzyl (S)-[1-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperidin-4-yl]carbamate (0.107 g, yield 28%) as a light yellow powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionadded methylene chloride (4 ml) and triethylamine (4 ml)
  3. stirringThe mixture was stirred at room temperature for 5 minutes
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in DMF (6 ml)
  6. stirringstirred at room temperature for 4 hours
  7. additionwas added
  8. stirringby stirring at room temperature overnight
  9. waitat 65° C. for 8 hours
  10. extractionthe solution was extracted with ethyl acetate twice
  11. washwashed with water
  12. dry with materiala saturated saline solution, dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationThe resulting filtrate was concentrated under reduced pressure
  15. customThe residue was purified by silica gel column chromatography (n-hexane/acetone=2/1)
  16. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-27247cd7d37a4c4b9a3a0df7522e45df
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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