Triethylamine → 4-(4-Bromo-2-fluorophenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 533521ノート

反応式

HRID 533521 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([S:15]([CH3:18])(=[O:17])=[O:16])([CH3:14])[C:11]([OH:13])=O)=[C:4]([F:19])[CH:3]=1.[O:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[O:26][NH2:27].O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>ClCCl.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([CH3:14])([S:15]([CH3:18])(=[O:17])=[O:16])[C:11]([NH:27][O:26][CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25][O:20]2)=[O:13])=[C:4]([F:19])[CH:3]=1

参加物

8

反応物 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 665779184-(4-Bromo-2-fluoro-phenyl)-2-methanesulfonyl-2-methyl-butyric acid

生成物 1

HCID 866687574-(4-Bromo-2-fluorophenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide収率 79.9%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

4-(4-Bromo-2-fluoro-phenyl)-2-methanesulfonyl-2-methyl-butyric acid (1.96 g, 5.55 mmol), O-tetrahydro-2H-pyran-2-yl-hydroxylamine (0.910 g, 7.77 mmol), 1-hydroxy benzotriazole monohydrate (1.53 g, 9.99 mmol), triethylamine (1.39 mL, 9.99 mmol) and 1, (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.49 g, 7.77 mmol) were combined followed by the addition 60 mL of dichloromethane. The reaction was allowed to stir at room temperature overnight, was then diluted with 20 mL of dichloromethane and 60 mL of water. The aqueous layer was re-extracted with DCM (2×40 mL). The organics were combined, dried over magnesium sulfate, filtered and concentrated onto silica gel. Silica chromatography (40% ethyl acetate 60% heptane to 40% ethyl acetate 60% heptane to 80% ethyl acetate 20% heptane for 60 minutes) afforded the title compound as a white foam 2.0 g, (79.9%). LC-MS m/z 452.1 (M−1)

後処理

  1. extractionThe aqueous layer was re-extracted with DCM (2×40 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated onto silica gel

出典と根拠

ORDレコード
ord-185b4f59ea054aeebe04b06c8fa276f7
出典データセット
uspto-grants-2014_10
特許番号
US08853258B2

反応ノート

読み込み中…