2-(Hydroxymethyl)-1H-benzimidazole → 1-(2-Trimethylsilylethoxymethyl)-2-hydroxymethylbenzimidazole

HRID 899724

Reaction equation

HRID 899724 reaction equation
[OH:1][CH2:2][C:3]1[NH:4][C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1.C(N(CC)C(C)C)(C)C.[CH3:21][Si:22]([CH3:29])([CH3:28])[CH2:23][CH2:24][O:25][CH2:26]Cl>CN(C=O)C>[CH3:21][Si:22]([CH3:29])([CH3:28])[CH2:23][CH2:24][O:25][CH2:26][N:7]1[C:6]2[CH:8]=[CH:9][CH:10]=[CH:11][C:5]=2[N:4]=[C:3]1[CH2:2][OH:1]

Participants

5

Reactant 3

HCID 785692-(Hydroxymethyl)-1H-benzimidazoleHCID 81531DiisopropylethylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl ether

Product 1

HCID 226099341-(2-Trimethylsilylethoxymethyl)-2-hydroxymethylbenzimidazoleYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 2-hydroxymethylbenzimidazole (31.94, 0.216 mol) in dry DMF (450 mL) was added N,N-diisopropylethylamine (90 mL, 0.52 mol) followed by 2-(trimethylsily)ethoxymethyl chloride (75% in pentane, 55 g, 0.25 mol) and the mixture heated to 60° C. for 2 h. The mixture was cooled to room temperature, concentrated under reduced pressure and partitioned between EtOAc (400 mL) and distilled water (700 mL). The phases were separated and the aqueous layer extracted with EtOAc (2×200 mL). The combined organic extracts were washed with brine (1×400 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. Purification of the crude oil by column chromatography on silica gel (4% MeOH/CH2Cl2) afforded the desired 1-(2-trimethylsilylethoxymethyl)-2-hydroxymethylbenzimidazole (26.28 g, 44%) as a yellow oil. 1H NMR (CDCl3) δ −0.04 (s, 9H), 0.89 (t, 2H, J=9 Hz), 1.75 (br s, 1H), 3.55 (t, 2H, J=9 Hz), 4.94 (s, 2H), 7.26-7.30 (m, 2H), 7.43-7.45 (m, 1H), 7.70-7.72 (m, 1H).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. custompartitioned between EtOAc (400 mL)
  4. distillationdistilled water (700 mL)
  5. customThe phases were separated
  6. extractionthe aqueous layer extracted with EtOAc (2×200 mL)
  7. washThe combined organic extracts were washed with brine (1×400 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customPurification of the crude oil by column chromatography on silica gel (4% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-c0919f52a99948a5bfe8cc74358ed2e2
Source dataset
uspto-grants-2008_04
Patent number
US07354934B2

Linked notes

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