Water → (S)-Tert-butyl (1-(5-(4-bromophenyl)-1H-imidazol-2-YL)-2-methylpropyl)carbamate

HRID 20883

反応式

HRID 20883 の反応式
BrCC(C1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][CH:6]=1)=O.[C:12]([NH:19][C@H:20]([C:24](O)=O)[CH:21]([CH3:23])[CH3:22])([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].CC[N:29]([CH:33]([CH3:35])[CH3:34])C(C)C.O.CC#[N:39]>C1(C)C=CC=CC=1>[Br:11][C:8]1[CH:9]=[CH:10][C:35]([C:33]2[NH:29][C:24]([C@@H:20]([NH:19][C:12](=[O:13])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH:21]([CH3:23])[CH3:22])=[N:39][CH:34]=2)=[CH:6][CH:7]=1

参加物

7

反応物 5

HCID 962WaterHCID 6342AcetonitrileHCID 74544-Bromophenacyl bromideHCID 81531DiisopropylethylamineHCID 83693Boc-L-Valine

生成物 1

HCID 59347642(S)-Tert-butyl (1-(5-(4-bromophenyl)-1H-imidazol-2-YL)-2-methylpropyl)carbamate収率 94%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

A solution of 2-bromo-1-(4-bromophenyl)ethanone (6.23 g, 22.3 mmol) and N-Boc-L-Valine (5.00 g, 23.0 mmol) in dry CH3CN (30 mL) was treated with iPr2NEt (4.40 mL, 25.3 mmol) and the solution was allowed to stir at rt overnight. The solvent was removed in vacuo and the resulting slurry was partitioned between EtOAc and H2O. The layers were separated and the aq phase was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give a yellow oil. LCMS: Anal. Calcd. for C18H24BrNO5: 413, 415; found: 412, 414 (M−H)−. The residue was suspended in toluene (60 mL) and NH4OAc (8.61 g, 111.7 mmol) was added. The mixture was heated reflux for 16 h with azeotropic removal of H2O (Dean-Stark). The mixture was cooled to rt and concentrated to dryness in vacuo. The residue was purified column chromatography (biotage) eluting with 10% MeOH in CH2Cl2 to afford the title compound (8.55 g, 94%) as a yellow foam. 1HNMR (500 MHz, CD3OD) δ 7.84 (s, 1H), 7.66 (app d, J=8.9 Hz, 2H), 7.64 (app d, J=8.9 Hz, 2H), 4.65 (d, J=7.7 Hz, 1H), 2.23-2.27 (m, 1H), 1.42 (s, 9H), 1.07 (d, J=6.5 Hz, 3H), 0.93 (d, J=6.5 Hz, 3H). LCMS: Anal. Calcd. for C18H24BrN3O2: 393, 395; found: 394, 396 (M+H)+.

後処理

  1. customThe solvent was removed in vacuo
  2. customthe resulting slurry was partitioned between EtOAc and H2O
  3. customThe layers were separated
  4. extractionthe aq phase was extracted with EtOAc
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a yellow oil
  9. temperatureThe mixture was heated
  10. temperatureThe mixture was cooled to rt
  11. concentrationconcentrated to dryness in vacuo
  12. customThe residue was purified column chromatography (biotage)
  13. washeluting with 10% MeOH in CH2Cl2

出典と根拠

ORDレコード
ord-bc8e34d0b6034badbde0add673fa3b9b
出典データセット
uspto-grants-2010_06
特許番号
US07745636B2

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