Sodium hydride → Tert-butyl 4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylate

HRID 2243845Notes

Reaction equation

HRID 2243845 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Br[C:22]1[N:23]([CH2:30][C:31]2([CH3:34])[CH2:33][O:32]2)[CH:24]=[C:25]([N+:27]([O-:29])=[O:28])[N:26]=1.[H-].[Na+]>CN(C=O)C.O>[C:17]([O:16][C:14]([N:11]1[CH2:12][CH2:13][N:8]([C:5]2[CH:6]=[CH:7][C:2]([O:1][CH2:33][C:31]3([CH3:34])[O:32][C:22]4=[N:26][C:25]([N+:27]([O-:29])=[O:28])=[CH:24][N:23]4[CH2:30]3)=[CH:3][CH:4]=2)[CH2:9][CH2:10]1)=[O:15])([CH3:20])([CH3:19])[CH3:18]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 116877404-(4-Hydroxy-phenyl)-piperazine-1-carboxylic acid tert-butyl esterHCID 85107489HCID 85107489, compound

Product 1

HCID 23081090Tert-butyl 4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperazine-1-carboxylateYield 88.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

tert-Butyl 4-(4-hydroxyphenyl)piperazine-1-carboxylate (1.5 g, 5.4 mmol) and 2-bromo-1-(2-methyl-oxiranylmethyl)-4-nitro-1H-imidazole (1.96 g, 7.5 mmol) are dissolved in DMF (100 ml) and sodium hydride (0.39 g, 9.7 mmol, 60% in mineral oil) is added at room temperature. Once gas evolution ceases the mixture is heated to 60° C. for 1 h. The mixture is cooled, diluted with water and extracted with ethyl acetate. The combined extracts are purified by silica gel chromatography (1% methanol in methylene chloride) to give 2.2 g (88%) of the product as a tan solid. ESI MS m/z 482 (M+Na+); 1H NMR (400 MHz, CDCl3) δ 7.58 (s, 1H), 6.87 (d, J=8.8 Hz, 2H), 6.78 (d, J=8.8 Hz, 2H), 4.48 (d, 10 Hz, 1H), 4.18 (d, J=10.4 Hz, 1H), 4.02 (t, J=9.2 Hz, 1H), 4.0-3.55 (m, 4H), 3.05-2.99 (m, 4H), 1.77 (s, 2H), 1.57 (s, 9H), 1.47 (s, 3H).

Workup

  1. temperatureThe mixture is cooled
  2. extractionextracted with ethyl acetate
  3. customThe combined extracts are purified by silica gel chromatography (1% methanol in methylene chloride)

Sources & evidence

ORD record
ord-e69fa6b8d6324c4a863d1e11526ec016
Source dataset
uspto-grants-2010_03
Patent number
US07678791B2

Reaction notes

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