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

HRID 899579

반응식

HRID 899579 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
60 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-18be2894ed674fa789a783219c3b5a22
출처 데이터셋
uspto-grants-2008_04
특허 번호
US07354932B2

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