Water → 4'-[2-Propoxy-5-(hydroxyiminomethyl)-4-vinylimidazol-1-ylmethyl]-3'-fluorobiphenyl-2-carboxylic acid t-butyl ester

HRID 341398ノート

反応式

HRID 341398 の反応式
[C:1]([O:5][C:6]([C:8]1[C:9]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][N:21]3[C:25]([CH:26]=O)=[C:24]([CH:28]=[CH2:29])[N:23]=[C:22]3[O:30][CH2:31][CH2:32][CH3:33])=[C:16]([F:34])[CH:15]=2)=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:36][OH:37].O>N1C=CC=CC=1>[C:1]([O:5][C:6]([C:8]1[C:9]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][N:21]3[C:25]([CH:26]=[N:36][OH:37])=[C:24]([CH:28]=[CH2:29])[N:23]=[C:22]3[O:30][CH2:31][CH2:32][CH3:33])=[C:16]([F:34])[CH:15]=2)=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

参加物

5

反応物 3

HCID 962WaterHCID 443297Hydroxyamine hydrochlorideHCID 598308974'-(2-Propoxy-5-formyl-4-vinylimidazol-1-ylmethyl)-3'-fluorobiphenyl-2-carboxylic acid t-butyl ester

生成物 1

HCID 725729564'-[2-Propoxy-5-(hydroxyiminomethyl)-4-vinylimidazol-1-ylmethyl]-3'-fluorobiphenyl-2-carboxylic acid t-butyl ester収率 99.6%

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

反応条件

温度
40 °C

実験手順

Intermediate (18b) (7.2 g, 15.5 mmol) was dissolved in pyridine (30 mL). Hydroxylamine hydrochloride (4.0 g, 57.9 mmol) was added followed by water (20 mL) and the mixture was stirred at 40° C. for 2 hours. The reaction was quenched with water, extracted with 200 mL EtOAc, washed with 3×100 mL 1M phosphoric acid, 1×100 mL saturated sodium bicarbonate solution, and 2×100 mL saturated aqueous NaCl, then dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (0-80% EtOAc:hexanes) to yield intermediate (18c) as a white solid (7.4 g). Anal. HPLC retention time=4.9 minutes. Gradient conditions: 25% solvent B/75% solvent A to 95% solvent B/5% solvent A over 6 minutes. MS m/z: [M+H+] calcd for C27H30FN3O4, 480.23; found 480.4. 1H-NMR (DMSO-d6) 10.99 (1H, s), 8.21 (1H, s), 7.67 (1H, d), 7.54 (1H, m), 7.44 (1H, s), 7.34 (1H, m), 7.11 (2H, m), 6.81 (2H, m), 5.73 (1H, d), 5.36 (2H, s), 5.10 (1H, d), 1.66 (2H, m), 1.13 (9H, s), 0.85 (4H, m).

後処理

  1. customThe reaction was quenched with water
  2. extractionextracted with 200 mL EtOAc
  3. washwashed with 3×100 mL 1M phosphoric acid, 1×100 mL saturated sodium bicarbonate solution, and 2×100 mL saturated aqueous NaCl
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by silica gel chromatography (0-80% EtOAc:hexanes)

出典と根拠

ORDレコード
ord-81dea7cb011341498ba2b26696e9f6fb
出典データセット
uspto-grants-2014_11
特許番号
US08895755B2

反応ノート

読み込み中…