3-Fluorophenol → Methyl 4-[(1S)-1-({[5-chloro-2-(3-fluorophenoxy)pyridin-3-yl]carbonyl}amino)ethyl]benzoate

HRID 1293190ノート

反応式

HRID 1293190 の反応式
Cl[C:2]1[C:7]([C:8]([NH:10][C@H:11]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=2)[CH3:12])=[O:9])=[CH:6][C:5]([Cl:23])=[CH:4][N:3]=1.[F:24][C:25]1[CH:26]=[C:27]([OH:31])[CH:28]=[CH:29][CH:30]=1.C(=O)(O)[O-].[Na+]>CN1CCCC1=O>[Cl:23][C:5]1[CH:6]=[C:7]([C:8]([NH:10][C@H:11]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=2)[CH3:12])=[O:9])[C:2]([O:31][C:27]2[CH:28]=[CH:29][CH:30]=[C:25]([F:24])[CH:26]=2)=[N:3][CH:4]=1

参加物

5

反応物 3

HCID 97433-FluorophenolHCID 516892Sodium BicarbonateHCID 86601543Methyl 4-((1S)-1-{[(2,5-dichloropyridin-3-yl)carbonyl]amino}ethyl)benzoate

生成物 1

HCID 69415945Methyl 4-[(1S)-1-({[5-chloro-2-(3-fluorophenoxy)pyridin-3-yl]carbonyl}amino)ethyl]benzoate収率 84%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
100 °C

実験手順

A mixture of methyl 4-((1S)-1-{[(2,5-dichloropyridin-3-yl)carbonyl]amino}ethyl)benzoate (step 1, 177 mg, 0.50 mmol), 3-fluorophenol (224 mg, 2.0 mmol) and sodium bicarbonate (105 mg, 1.25 mmol) in 1-methylpyrrolidin-2-one (2 mL) was stirred at 100° C. for 24 h. After cooling, the reaction mixture was partitioned between water (50 mL) and dichloromethane (50 mL) and the organic phase was separated. The aqueous phase was extracted with dichloromethane (50 mL). The combined organic layer was washed with brine (100 mL), dried (sodium sulfate), and concentrated. The residue was purified by flash column chromatography on silica gel (10 g) eluting with hexane/ethyl acetate (4/1) to afford 180 mg (84%) of the title compound as white solids: 1H-NMR (CDCl3) δ 8.55 (1H, d, J=2.7 Hz), 8.15 (1H, d, J=2.7 Hz), 8.07–7.98 (3H, m), 7.47–7.37 (3H, m), 7.07–6.99 (1H, m), 6.98–6.88 (2H, m), 5.42–5.31 (1H, m), 3.90 (3H, s), 1.60 (3H, d, J=7.0 Hz); MS (ESI) m/z 429 (M+H)+, 427 (M−H)−.

後処理

  1. temperatureAfter cooling
  2. customthe reaction mixture was partitioned between water (50 mL) and dichloromethane (50 mL)
  3. customthe organic phase was separated
  4. extractionThe aqueous phase was extracted with dichloromethane (50 mL)
  5. washThe combined organic layer was washed with brine (100 mL)
  6. dry with materialdried (sodium sulfate)
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography on silica gel (10 g)
  9. washeluting with hexane/ethyl acetate (4/1)

出典と根拠

ORDレコード
ord-9a58d41cf70d43e28578c1fa67b1fc58
出典データセット
uspto-grants-2007_07
特許番号
US07238714B2

反応ノート

読み込み中…