Trifluoroacetic acid → (R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxybenzyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole

HRID 856229Notes

Reaction equation

HRID 856229 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][N:24]([C:27](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.FC(F)(F)C(O)=O.[F:41][C:42]([F:53])([F:52])[O:43][C:44]1[CH:51]=[CH:50][C:47](C=O)=[CH:46][CH:45]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl>[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][N:24]([CH2:27][C:47]4[CH:46]=[CH:45][C:44]([O:43][C:42]([F:41])([F:52])[F:53])=[CH:51][CH:50]=4)[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

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 69573p-(Trifluoromethoxy)benzaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 67274388tert-butyl (R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylate

Product 1

HCID 10459740(R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxybenzyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazoleYield 63.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Tert-butyl (R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]-piperazine-1-carboxylate prepared in Example 148 (4.22 g, 9.60 mmol) was dissolved in methylene chloride (10 ml). To the solution, trifluoroacetic acid (30 ml) was added followed by stirring at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure and added methylene chloride (10 ml) and triethylamine (10 ml). The solution was stirred at room temperature for 5 minutes and then concentrated under reduced pressure. The residue was dissolved in dichloroethane. To the solution, 4-trifluoromethoxybenzaldehyde (1.64 ml, 11.5 mmol) and sodium triacetoxyborohydride (3.05 g, 14.4 mmol) were added with cooling on ice-bath followed by stirring at room temperature overnight. To the reaction mixture, a saturated sodium hydrogencarbonate solution and methylene chloride were added, and the solution was stirred and extracted with methylene chloride. The organic phase was 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 then crystallized from methylene chloride-ethyl acetate to afford (R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxybenzyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole (3.23 g, yield 63%) as a light yellow powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionadded methylene chloride (10 ml) and triethylamine (10 ml)
  3. stirringThe solution was stirred at room temperature for 5 minutes
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in dichloroethane
  6. temperaturewith cooling on ice-bath
  7. stirringby stirring at room temperature overnight
  8. stirringthe solution was stirred
  9. extractionextracted with methylene chloride
  10. dry with materialThe organic phase was dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationThe resulting filtrate was concentrated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1)
  14. customcrystallized from methylene chloride-ethyl acetate

Sources & evidence

ORD record
ord-a12a25db4125423ea4548570b4dc20e0
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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