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

HRID 856232Notes

Reaction equation

HRID 856232 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: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.[F:48][C:49]([F:61])([F:60])[O:50][C:51]1[CH:59]=[CH:58][C:54](C(Cl)=O)=[CH:53][CH:52]=1>C(Cl)Cl.O>[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:28])[C:54]4[CH:53]=[CH:52][C:51]([O:50][C:49]([F:48])([F:60])[F:61])=[CH:59][CH:58]=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 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 1421104-(Trifluoromethoxy)benzoyl ChlorideHCID 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 69480550(R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxybenzoyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazoleYield 74%

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 5 hours. The reaction mixture was concentrated under reduced pressure and added methylene chloride (10 ml), triethylamine (2 ml) and 4-trifluoromethoxybenzoyl chloride (0.15 ml, 0.98 mmol). The reaction mixture was stirred at room temperature for 1 hour, then 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/ethyl acetate=10/1) and crystallized from methylene chloride-diisopropyl ether to afford (R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxybenzoyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole (263 mg, yield 74%) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. stirringThe reaction mixture was stirred 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/ethyl acetate=10/1)
  9. customcrystallized from methylene chloride-diisopropyl ether

Sources & evidence

ORD record
ord-7689ea5695164cb3b868ca25266b6dd7
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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