Trifluoroacetic acid → ethyl(R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylate

HRID 856227Notes

Reaction equation

HRID 856227 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]([O:29][C:30](C)(C)[CH3:31])=[O:28])[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.C(N(CC)CC)C.ClC(OCC)=O>C(Cl)Cl.O>[CH3:1][C@@:2]1([CH2:13][O:14][C:15]2[CH:16]=[CH:17][C:18]([N:21]3[CH2:22][CH2:23][N:24]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:25][CH2:26]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

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 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 69635299ethyl(R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylateYield 65%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 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 (300 mg, 0.65 mmol) was dissolved in methylene chloride (5 ml). To the solution, trifluoroacetic acid (5 ml) was added followed by stirring at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure and then added methylene chloride (5 ml), triethylamine (2 ml) and ethyl chloroformate (0.11 ml, 1.31 mmol) followed by stirring at room temperature for 1 hour. The reaction mixture was poured into water and extracted with methylene chloride. 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 ethyl (R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylate (182 mg, yield 65%) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. stirringby stirring at room temperature for 1 hour
  3. extractionextracted with methylene chloride
  4. washThe organic phase was washed with a saturated saline solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationThe resulting filtrate was concentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1)
  9. customcrystallized from methylene chloride-isopropyl ether

Sources & evidence

ORD record
ord-6c0310853fa8414cab811a6e937fd912
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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