Sodium Iodide → 5-(2-{4-[5-(4-Fluoro-phenyl)-4-methoxymethyl-oxazol-2-yl]-piperidin-1-yl}-ethyl)-2-methoxy-benzenesulfonamide

HRID 2288997ノート

反応式

HRID 2288997 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[CH2:19][O:20][CH3:21])=[CH:4][CH:3]=1.Cl[CH2:23][CH2:24][C:25]1[CH:26]=[CH:27][C:28]([O:35][CH3:36])=[C:29]([S:31]([NH2:34])(=[O:33])=[O:32])[CH:30]=1.[I-].[Na+].C(N(C(C)C)CC)(C)C>O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH:13]3[CH2:14][CH2:15][N:16]([CH2:23][CH2:24][C:25]4[CH:26]=[CH:27][C:28]([O:35][CH3:36])=[C:29]([S:31]([NH2:34])(=[O:32])=[O:33])[CH:30]=4)[CH2:17][CH2:18]3)=[N:10][C:9]=2[CH2:19][O:20][CH3:21])=[CH:4][CH:3]=1

参加物

6

反応物 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 187004064-[5-(4-Fluoro-Phenyl)-4-Methoxymethyl-Oxazol-2-yl]-PiperidineHCID 187004435-(2-Chloroethyl)-2-methoxy-benzenesulfonamide

生成物 1

HCID 187004405-(2-{4-[5-(4-Fluoro-phenyl)-4-methoxymethyl-oxazol-2-yl]-piperidin-1-yl}-ethyl)-2-methoxy-benzenesulfonamide収率 40%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

A solution of 4-[5-(4-fluoro-phenyl)-4-methoxymethyl-oxazol-2-yl]-piperidine (0.3 g; 1.03 mmol) in dry dioxane (7 ml) is treated with 5-(2-chloroethyl)-2-methoxy-benzenesulfonamide (0.52 g; 2.06 mmol), sodium iodide (0.31 g; 2.06 mmol) and diisopropylethylamine (0.72 ml; 4.12 mmol) and heated to 100 C. for 16 hours. The reaction mixture is partitioned between ethyl acetate (50 ml) and dilute sodium bicarbonate (20 ml). The aqueous phase is washed with ethyl acetate (20 ml). The combined organic phases are washed with saturated brine (10 ml), dried over sodium sulfate and concentrated to dryness. Purification by radial chromatography on silica gel using a methanol/ethyl acetate gradient (5%-20%) is followed by a second chromatography using a methanol/dichloromethane gradient (5%-15%). Crystallization from dichloromethane/ethyl acetate afforded the product as a white solid (0.20 g; 40%). HNMR (CDCl3): 7.72 (d, 1H, J=2.1 Hz), 7.62 (m, 2H), 7.35 (dd, 1H, J=8.6; 2.1 Hz), 7.13 (t, 21H, J=8.6 Hz), 6.96 (d, 1H, J=8.6 Hz), 5.64 (broad s, 2H), 4.44 (s, 2H), 3.97 (s, 3H), 3.44 (s, 3H), 2.96 (m, 2H), 2.80 (m, 1H), 2.75 (m, 2H), 2.53 (m, 2H), 2.10 (m, 4H), 1.90 (m, 2H). Mass spectrum: m/e calculated (MH+)=504; observed (MH+)=504.

後処理

  1. temperatureheated to 100 C
  2. customThe reaction mixture is partitioned between ethyl acetate (50 ml) and dilute sodium bicarbonate (20 ml)
  3. washThe aqueous phase is washed with ethyl acetate (20 ml)
  4. washThe combined organic phases are washed with saturated brine (10 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness
  7. customPurification by radial chromatography on silica gel using a methanol/ethyl acetate gradient (5%-20%)
  8. customCrystallization from dichloromethane/ethyl acetate

出典と根拠

ORDレコード
ord-15f4c31937b64230bc5d2a5da91c81f3
出典データセット
uspto-grants-2000_07
特許番号
US06090825

反応ノート

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