Sodium hydride → 2-(4-Tert-butoxycarbonylpiperazin-1-yl)methyl-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole

HRID 2243849Notes

Reaction equation

HRID 2243849 reaction equation
CC1(CN2C=C([N+]([O-])=O)N=C2)CO1.C(OC(N1CCNCC1)=O)(C)(C)C.[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][N:37]([CH2:40][C:41]([OH:53])([CH3:52])[CH2:42][N:43]2[CH:47]=[C:46]([N+:48]([O-:50])=[O:49])[N:45]=[C:44]2Br)[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28].[H-].[Na+]>CC(O)C.CN(C=O)C.O>[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][N:37]([CH2:40][C:41]2([CH3:52])[O:53][C:44]3=[N:45][C:46]([N+:48]([O-:50])=[O:49])=[CH:47][N:43]3[CH2:42]2)[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 686533884-[3-(2-Bromo-4-nitro-imidazol-1-yl)-2-hydroxy-2-methyl-propyl]-piperazine-1-carboxylic acid tert-butyl esterHCID 866206311-(2-methyl-oxiranylmethyl)-4-nitro-1H-imidazole

Product 1

HCID 230810802-(4-Tert-butoxycarbonylpiperazin-1-yl)methyl-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazoleYield 50.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 1-(2-methyl-oxiranylmethyl)-4-nitro-1H-imidazole (1.5 g, 5.72 mmol) and piperazine-1-carboxylic acid tert-butyl ester (1.1 g, 5.72 mmol) is dissolved in IPA and heated to 60° C. for 24 h. The solution is concentrated and partitioned between water and ethyl acetate. The organic layer is dried over sodium sulfate and concentrated. The resulting solution of 4-[3-(2-bromo-4-nitro-imidazol-1-yl)-2-hydroxy-2-methyl-propyl]-piperazine-1-carboxylic acid tert-butyl ester (1.1 g, 2.46 mmol) in DMF (15 ml) was treated with sodium hydride (148 mg, 3.69 mmol) and stirred for 3 h at 60° C. The mixture was diluted with water and extracted with ethyl acetate. The organic layer is dried over sodium sulfate and concentrated. The residue is purified by silica gel chromatography to give 4-(2-methyl-6-nitro-2,3-dihydro-imidazo[2,1-b]oxazol-2-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (453 mg, 50%) of as a light yellow oil. ESI MS m/z 367 (M+Na+); 1H NMR (400 MHz, CDCl3) δ 7.54 (s, 1H), 4.30 (d, J=10 Hz, 1H), 3.92 (d, J=10 Hz, 1H), 3.45-3.02 (m, 4H), 2.86 (d, J=14.8 Hz, 1H), 2.70-2.39 (m, 4H), 2.55 (d, J=14.8, 1H), 1.58 (s, 3H), 1.45 (s, 9H).

Workup

  1. concentrationThe solution is concentrated
  2. custompartitioned between water and ethyl acetate
  3. dry with materialThe organic layer is dried over sodium sulfate
  4. concentrationconcentrated
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic layer is dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue is purified by silica gel chromatography

Sources & evidence

ORD record
ord-f62c75ffb03e47df9d72b2a1ec70b4e9
Source dataset
uspto-grants-2010_03
Patent number
US07678791B2

Reaction notes

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