Imidazole → 4-(4-bromophenyl)-1-(1H-imidazol-1-yl)-2-butanol hydrochloride

HRID 549370Notes

Reaction equation

HRID 549370 reaction equation
[H-].[Na+].CN(C=O)C.[NH:8]1[CH:12]=[CH:11][N:10]=[CH:9]1.[Br:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][CH:22]2[O:24][CH2:23]2)=[CH:16][CH:15]=1>O>[Br:13][C:14]1[CH:15]=[CH:16][C:17]([CH2:20][CH2:21][CH:22]([OH:24])[CH2:23][N:8]2[CH:12]=[CH:11][N:10]=[CH:9]2)=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 536320112-[2-(4-Bromophenyl)ethyl]oxirane

Product 1

HCID 202827674-(4-bromophenyl)-1-(1H-imidazol-1-yl)-2-butanol hydrochlorideYield 84.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent3×

Conditions

Temperature
0 °C

Procedure

To a sample of pure sodium hydride (1.60 g, 66.58 mmol, 1.4 equiv) under a N2 atmosphere was added DMF (40 mL). The mixture was cooled to 0° C. and imidazole (4.86 g, 71.34 mmol, 1.5 equiv) was added in many small portions over 1 h. Stirring was continued for an additional 0.5 h at 0° C. To the mixture was added dropwise the neat epoxide 12a (10.80 g, 47.56 mmol, 1 equiv); the epoxide container was rinsed with DMF (10 mL) and the rinse solution was added to the reaction mixture. The mixture was stirred at 0° C. for 0.5 h and then at rt for 24 h. Monitoring by TLC (silica gel, EtOAc) confirmed the completion of the reaction. Water (20 mL) was added, the mixture cooled to 0° C., and more water (200 mL) was added without stirring. After 1 h at 0° C. an additional 100 mL of water were added. The white solid was removed by filtration and washed with water (3×250 mL), and then with hexanes (200 mL). High-vacuum drying gave the imidazole-alcohol 13a (11.80 g, 39.98 mmol, 84%) as a white solid: mp 121-122° C., Rf=0.08 (ethyl acetate); 1H NMR (400 MHz, CDCl3): δ 1.68-1.82 (m, 2H), 2.68-2.76 (m, 1H), 2.82-2.89 (m, 1H), 3.75-3.94 (m, 3H), 6.80 (s, 1H), 6.84 (s, 1H), 7.08 (d, J=8.4 Hz, 2H), 7.31 (s, 1H), 7.40 (d, J=8.4 Hz, 2H); 13C NMR (100 Adz, CDCl3): δ 31.3, 36.0, 54.1, 69.5, 119.9, 128.5, 130.4, 131.6, 140.6; HAS (EI) Calcd. for C13H15BrN2O: 294.0368 (M+). Found: 294.0375.

Workup

  1. washthe epoxide container was rinsed with DMF (10 mL)
  2. additionthe rinse solution was added to the reaction mixture
  3. stirringThe mixture was stirred at 0° C. for 0.5 h
  4. waitat rt for 24 h
  5. customthe completion of the reaction
  6. temperaturethe mixture cooled to 0° C.
  7. stirringwithout stirring
  8. customThe white solid was removed by filtration
  9. washwashed with water (3×250 mL)
  10. customHigh-vacuum drying

Sources & evidence

ORD record
ord-a65d0039dfcf4ee7b8d5e3a351e453ab
Source dataset
uspto-grants-2011_05
Patent number
US07943650B2

Reaction notes

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