Hydrochloric Acid → 2-Methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl piperidine-1-carboxylate

HRID 856189Notes

Reaction equation

HRID 856189 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ClC(Cl)(O[C:11](=[O:17])[O:12][C:13](Cl)(Cl)Cl)Cl.O[CH2:20][C:21]1(C)[O:25][C:24]2=[N:26][C:27]([N+:29]([O-:31])=[O:30])=[CH:28][N:23]2[CH2:22]1.N1CCCCC1.Cl>C(Cl)Cl>[N:1]1([C:11]([O:12][CH2:13][C:21]2([CH3:20])[O:25][C:24]3=[N:26][C:27]([N+:29]([O-:31])=[O:30])=[CH:28][N:23]3[CH2:22]2)=[O:17])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 8082PiperidineHCID 94429TriphosgeneHCID 23081240(2-Methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-yl)methanol

Product 1

HCID 230813602-Methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl piperidine-1-carboxylateYield 34.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Pyridine (0.37 ml, 4.5 mmol) and triphosgene (0.18 g, 0.6 mmol) were added to a suspension of 2-hydroxymethyl-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole prepared in Example 33 (0.3 g, 1.5 mmol) in methylene chloride (15 ml) with cooling on ice-bath followed by stirring at room temperature for 2 hours. The reaction mixture was cooled on ice-bath and added piperidine (0.16 ml, 1.7 mmol). The resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was cooled on ice-bath and added 10% hydrochloric acid, and the insoluble matters were removed by filtration. The filtrate was extracted with methylene chloride, and the organic phase was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=3/2) and recrystallized from methylene chloride-diisopropyl ether to afford 2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl piperidine-1-carboxylate (65 mg, yield 14%) as a white solid.

Workup

  1. temperaturewith cooling on ice-bath
  2. temperatureThe reaction mixture was cooled on ice-bath
  3. stirringThe resulting mixture was stirred at room temperature for 3 hours
  4. temperatureThe reaction mixture was cooled on ice-bath
  5. customthe insoluble matters were removed by filtration
  6. extractionThe filtrate was extracted with methylene chloride
  7. dry with materialthe organic phase was dried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=3/2)
  10. customrecrystallized from methylene chloride-diisopropyl ether

Sources & evidence

ORD record
ord-46c60a01b7b64827adb9625fb18ffed2
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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