Triethylamine → 4-(4-Fluoro-3-methoxy-benzylcarbamoyl)-benzenesulfonyl chloride

HRID 737016ノート

反応式

HRID 737016 の反応式
[Cl:1][S:2]([C:5]1[CH:13]=[CH:12][C:8]([C:9](Cl)=[O:10])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[F:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][NH2:20])=[CH:17][C:16]=1[O:23][CH3:24].CCN(CC)CC>C1COCC1.CN(C1C=CN=CC=1)C>[F:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][NH:20][C:9]([C:8]2[CH:12]=[CH:13][C:5]([S:2]([Cl:1])(=[O:4])=[O:3])=[CH:6][CH:7]=2)=[O:10])=[CH:17][C:16]=1[O:23][CH3:24]

参加物

6

反応物 3

HCID 8471TriethylamineHCID 820244-(Chlorosulphonyl)benzoyl chlorideHCID 442031244-Fluoro-3-methoxybenzylamine

生成物 1

HCID 589751944-(4-Fluoro-3-methoxy-benzylcarbamoyl)-benzenesulfonyl chloride収率 30.9%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

Dissolve 4-chlorosulfonyl-benzoyl chloride (3.18 g, 13.3 mmol) in THF (25 mL) and cool to −78° C. Slowly add a pre-mixed solution of 4-fluoro-3-methoxybenzyl-amine (1.91 g, 12.3 mmol), Et3N (1.64 mL, 11.8 mmol), and DMAP (150 mg, 1.23 mmol) in THF (25 mL) to the above cooled solution over 1 h. Stir the resulting mixture at −78° C. for 1 h, then warm to RT and stir for 4 h. Remove all solids by filtration and wash with THF (5 mL). Concentrate the filtrate and re-dissolve the crude material in EtOAc (30 mL) and wash with 1N HCl (30 mL). Separate the organic and aqueous layers and extract the aqueous phase with additional EtOAc (30 mL). Combine the organic solutions dry, filter, and concentrate. Purify the crude material by flash chromatography, using a linear gradient of 100% hexanes to 40% EtOAc/hexanes) to give the title compound as a white solid (1.36 g, 28%). MS (ES−) 356.1 (M−1)−. 1H NMR (400 MHz, CDCl3): δ 8.11 (d, 2H, J=8.3), 8.00 (d, 2H, J=8.8), 7.05 (dd, 1H, J=8.2, 11.1), 6.96 (dd, 1H, J=1.9, 8.0), 6.86 (m, 1H), 6.44 (br s, 1H), 4.61 (d, 2H, J=5.7), 3.88 (s, 3H).

後処理

  1. temperaturewarm to RT
  2. stirringstir for 4 h
  3. customRemove all solids
  4. filtrationby filtration
  5. washwash with THF (5 mL)
  6. concentrationConcentrate the filtrate
  7. dissolutionre-dissolve the crude material in EtOAc (30 mL)
  8. washwash with 1N HCl (30 mL)
  9. customSeparate the organic and aqueous layers
  10. extractionextract the aqueous phase with additional EtOAc (30 mL)
  11. customCombine the organic solutions dry
  12. filtrationfilter
  13. concentrationconcentrate
  14. customPurify the crude material by flash chromatography

出典と根拠

ORDレコード
ord-069298082eef4447995ede85896939bd
出典データセット
uspto-grants-2009_09
特許番号
US07595339B2

反応ノート

読み込み中…