Imidazole → 6-(2-Imidazole-1-yl-ethoxy)-3,4-dihydro-2H-naphthalen-1-one

HRID 1386365Notes

Reaction equation

HRID 1386365 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[CH:6][N:5]=[CH:4]1.Cl[CH2:9][CH2:10][O:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[C:18](=[O:22])[CH2:17][CH2:16][CH2:15]2>CN(C=O)C>[N:3]1([CH2:9][CH2:10][O:11][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[C:18](=[O:22])[CH2:17][CH2:16][CH2:15]3)[CH:7]=[CH:6][N:5]=[CH:4]1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 24758Sodium hydrideHCID 120429826-(beta-Chloroethoxy)-1-tetralone

Product 1

HCID 154869126-(2-Imidazole-1-yl-ethoxy)-3,4-dihydro-2H-naphthalen-1-oneYield 67.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of NaH (0.29 g, 7.2 mmol, 60% oil dispersion prewashed with dry hexanes) in 18 mL of dry DMF under a nitrogen flow was cooled to 0° C. and imidazole (0.49 g, 7.2 mmol) was added portionwise. The ice bath was removed and the reaction stirred at room temperature 20 minutes. The reaction was cooled to 0° C. and a solution of 6-(β-chloroethoxy)-1-tetralone (1.07 g, 4.8 mmol) in 12 mL of dry DMF was added over several minutes. The ice bath was removed and the reaction stirred at room temperature overnight. The reaction was partitioned between 20 mL of water and 200 mL of EtOAc. The organic portion was removed, and the aqueous portion was extracted with EtOAc (5×50 mL). The combined extracts were washed successively with water and brine, dried, filtered, and concentrated under vacuum to afford 1.6 g of crude product. Purification by flash chromatography (silica gel, 130 g, 8% MeOH in DCM) afforded 0.83 g (67%) of an off-white crystalline solid: CI-MS m/e 256 (M+), 257 (M++1);

Workup

  1. customThe ice bath was removed
  2. temperatureThe reaction was cooled to 0° C.
  3. customThe ice bath was removed
  4. stirringthe reaction stirred at room temperature overnight
  5. customThe reaction was partitioned between 20 mL of water and 200 mL of EtOAc
  6. customThe organic portion was removed
  7. extractionthe aqueous portion was extracted with EtOAc (5×50 mL)
  8. washThe combined extracts were washed successively with water and brine
  9. customdried
  10. filtrationfiltered
  11. concentrationconcentrated under vacuum
  12. customto afford 1.6 g of crude product
  13. customPurification by flash chromatography (silica gel, 130 g, 8% MeOH in DCM)

Sources & evidence

ORD record
ord-618a3bb078ef417fa5613e536e926f24
Source dataset
uspto-grants-2001_07
Patent number
US06265422B1

Reaction notes

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