Trifluoroacetic acid → HCID 5278893, compound

HRID 1695970Notes

Reaction equation

HRID 1695970 reaction equation
[CH3:1][C@@:2]1([CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:26][CH2:25][CH:24]([N:27]([CH3:35])[C:28](OC(C)(C)C)=O)[CH2:23][CH2:22]3)=[CH:17][CH:16]=2)[O:6][C:5]2=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]2[CH2:3]1.[F:36][C:37]([F:42])([F:41])[C:38](O)=O>ClCCl>[CH3:1][C@@:2]1([CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:22][CH2:23][CH:24]([N:27]([CH3:35])[CH2:28][C:19]4[CH:20]=[CH:15][CH:16]=[CH:17][C:38]=4[C:37]([F:42])([F:41])[F:36])[CH2:25][CH2:26]3)=[CH:17][CH:16]=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

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67274258HCID 67274258, compound

Product 1

HCID 5278893HCID 5278893, compoundYield 52.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

0.80 g of (R)-2-methyl-2-(4-(4-(N-methyl-N-tert-butoxycarbonylamino)piperidin-1-yl)phenoxymethyl)-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole was dissolved in 2 ml of trifluoroacetic acid and 2 ml of dichloromethane, followed by stirring at room temperature for 15 hours. Thereafter, the reaction solution was concentrated under a reduced pressure, and then, 2 ml of dichloromethane and 2 ml of triethylamine were added thereto. The mixture was stirred at room temperature for 5 minutes, and it was then concentrated under a reduced pressure. The residue was dissolved in 8 ml of dichloroethane, and then, 0.57 g of 2-trifluoromethylbenzaldehyde and 0.70 g of triacetoxy sodium borohydride were added thereto while cooled by ice. The mixture was warmed to room temperature, and the mixture was then stirred for 24 hours. Thereafter, an aqueous solution of potassium carbonate and dichloromethane were added to the reaction solution. The mixture was stirred, and then extracted with dichloromethane. The organic layer was dried over magnesium sulfate, and then filtered. The obtained filtrate was concentrated under a reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane:methanol=9:1). The resultant product was then crystallized from ethyl acetate to obtain 0.47 g (yield: 52.4%) of light yellow powders, (R)-2-methyl-2-(4-(4-(N-methyl-N-(2-trifluoromethylbenzyl)amino)piperidin-1-yl)phenoxymethyl)-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole.

Workup

  1. concentrationThereafter, the reaction solution was concentrated under a reduced pressure
  2. addition2 ml of dichloromethane and 2 ml of triethylamine were added
  3. stirringThe mixture was stirred at room temperature for 5 minutes
  4. concentrationit was then concentrated under a reduced pressure
  5. dissolutionThe residue was dissolved in 8 ml of dichloroethane
  6. addition0.57 g of 2-trifluoromethylbenzaldehyde and 0.70 g of triacetoxy sodium borohydride were added
  7. temperaturewhile cooled by ice
  8. temperatureThe mixture was warmed to room temperature
  9. stirringthe mixture was then stirred for 24 hours
  10. additionThereafter, an aqueous solution of potassium carbonate and dichloromethane were added to the reaction solution
  11. stirringThe mixture was stirred
  12. extractionextracted with dichloromethane
  13. dry with materialThe organic layer was dried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationThe obtained filtrate was concentrated under a reduced pressure
  16. customThe residue was purified by silica gel column chromatography (dichloromethane:methanol=9:1)
  17. customThe resultant product was then crystallized from ethyl acetate

Sources & evidence

ORD record
ord-adba0ec38fe04447821d0e75b437c326
Source dataset
uspto-grants-2012_04
Patent number
US08163753B2

Reaction notes

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