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

HRID 1624227

反応式

HRID 1624227 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

HCID 226099341-(2-Trimethylsilylethoxymethyl)-2-hydroxymethylbenzimidazole収率 44%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

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), 5.58 (s, 2H), 7.26-7.30 (m, 2H), 7.43-7.45 (m, 1H), 7.70-7.72 (m, 1H).

後処理

  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)

出典と根拠

ORDレコード
ord-18c22a386820436b908d5ef663f39a0d
出典データセット
uspto-grants-2014_07
特許番号
US08778967B2

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