Trifluoroacetic acid → HCID 5278921, compound

HRID 1695972Notes

Reaction equation

HRID 1695972 reaction equation
[CH3:1][C@@:2]1([CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][C:24]([N:27]4[CH2:32][CH2:31][N:30]([C:33](OC(C)(C)C)=O)[CH2:29][CH2:28]4)=[CH:23][CH: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:40][C:41]([F:46])([F:45])[C:42](O)=O>ClCCl>[CH3:1][C@@:2]1([CH2:13][O:14][C:15]2[CH:16]=[CH:17][C:18]([C:21]3[CH:22]=[CH:23][C:24]([N:27]4[CH2:32][CH2:31][N:30]([CH2:33][C:15]5[CH:20]=[CH:19][C:42]([C:41]([F:46])([F:45])[F:40])=[CH:17][CH:16]=5)[CH2:29][CH2:28]4)=[CH:25][CH:26]=3)=[CH:19][CH:20]=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 67276101HCID 67276101, compound

Product 1

HCID 5278921HCID 5278921, compoundYield 60.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

790 mg of (R)-2-methyl-2-(4′-(4-tert-butoxycarbonylpiperazin-1-yl)biphenyl-4-yloxymethyl)-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole was dissolved in 10 ml of trifluoroacetic acid and 5 ml of dichloromethane, followed by stirring at room temperature overnight. Thereafter, the reaction solution was concentrated under a reduced pressure, and then, 6 ml of dichloromethane and 6 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 15 ml of DMF, and then, 0.4 ml of 4-trifluoromethylbenzaldehyde and 625 mg of triacetoxy sodium borohydride were added thereto while cooled by ice, followed by stirring at room temperature overnight. Thereafter, water was added to the reaction solution, the mixture was stirred, and the insoluble precipitate was removed by filtration. The filtrate was washed with water and then dissolved in dichloromethane. The obtained solution was washed with a saturated aqueous solution of sodium chloride, and then dried over sodium sulfate. The sodium sulfate was filtered, and the filtrate was concentrated under a reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane:methanol=20:1). The resultant product was then recrystallized from a mixed solvent consisting of dichloromethane and ethyl acetate to obtain 585 mg (yield: 60.5%) of light yellow powders, (R)-2-methyl-6-nitro-2-(4′-(4-(4-trifluoromethylbenzyl)piperazin-1-yl)biphenyl-4-yloxymethyl)-2,3-dihydroimidazo[2,1-b]oxazole.

Workup

  1. concentrationThereafter, the reaction solution was concentrated under a reduced pressure
  2. addition6 ml of dichloromethane and 6 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 15 ml of DMF
  6. addition0.4 ml of 4-trifluoromethylbenzaldehyde and 625 mg of triacetoxy sodium borohydride were added
  7. temperaturewhile cooled by ice
  8. stirringby stirring at room temperature overnight
  9. additionThereafter, water was added to the reaction solution
  10. stirringthe mixture was stirred
  11. customthe insoluble precipitate was removed by filtration
  12. washThe filtrate was washed with water
  13. dissolutiondissolved in dichloromethane
  14. washThe obtained solution was washed with a saturated aqueous solution of sodium chloride
  15. dry with materialdried over sodium sulfate
  16. filtrationThe sodium sulfate was filtered
  17. concentrationthe filtrate was concentrated under a reduced pressure
  18. customThe residue was purified by silica gel column chromatography (dichloromethane:methanol=20:1)
  19. customThe resultant product was then recrystallized from a mixed solvent

Sources & evidence

ORD record
ord-fdd615d828f84ddf8d3da0c31dfc73d2
Source dataset
uspto-grants-2012_04
Patent number
US08163753B2

Reaction notes

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