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

HRID 856228Notes

Reaction equation

HRID 856228 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(C)(C)C)=[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.[Cl:41][C:42]1[CH:49]=[CH:48][C:45]([CH2:46]O)=[CH:44][CH:43]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>C(Cl)Cl.CN(C=O)C.O>[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][N:24]([C:27]([O:29][CH2:46][C:45]4[CH:48]=[CH:49][C:42]([Cl:41])=[CH:43][CH:44]=4)=[O:28])[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

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 133974-Chlorobenzyl alcoholHCID 682631,1'-CarbonyldiimidazoleHCID 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 696352304-chlorobenzyl (R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylateYield 91.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

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 (2 ml) and triethylamine (2 ml). After stirring at room temperature for 5 minutes, the solution was concentrated under reduced pressure, and the residue was dissolved in DMF (15 ml). To the solution, a mixture of 4-chlorobenzyl alcohol (186 mg, 1.31 mmol), 1,1′-carbonyldiimidazole (212 mg, 1.31 mmol) in DMF (5 ml) stirred at room temperature for 3 hours was added followed by stirring at room temperature overnight. The reaction mixture was poured into water, extracted from ethyl acetate, and 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 4-chlorobenzyl (R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylate (313 mg, yield 91%) as a light yellow powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. stirringAfter stirring at room temperature for 5 minutes
  3. concentrationthe solution was concentrated under reduced pressure
  4. dissolutionthe residue was dissolved in DMF (15 ml)
  5. stirringstirred at room temperature for 3 hours
  6. additionwas added
  7. stirringby stirring at room temperature overnight
  8. extractionextracted from ethyl acetate
  9. washthe organic phase was washed with a saturated saline solution
  10. dry with materialdried 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-isopropyl ether

Sources & evidence

ORD record
ord-f8ab1e44625f45238fe53dd7920faa90
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

Loading…