Methyl iodide → HCID 178499284、化合物

HRID 1694443ノート

反応式

HRID 1694443 の反応式
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH:28]=2)=[CH:8][C:9]=1[N:10]([C@H:20]1[CH2:25][CH2:24][C@H:23]([OH:26])[CH2:22][CH2:21]1)[C:11]([C@H:13]1[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4].I[CH3:34].[H-].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH:28]=2)=[CH:8][C:9]=1[N:10]([C@H:20]1[CH2:25][CH2:24][C@H:23]([O:26][CH3:34])[CH2:22][CH2:21]1)[C:11]([C@H:13]1[CH2:14][CH2:15][C@H:16]([CH3:19])[CH2:17][CH2:18]1)=[O:12])=[O:4]

参加物

5

反応物 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178499281HCID 178499281、化合物

生成物 1

HCID 178499284HCID 178499284、化合物収率 83%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To a solution of 5-cyclohex-1-enyl-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (1.007 g, 2.19 mmol) in dry DMF was added iodomethane (4.10 mL, 65.7 mmol), the mixture was cooled to 0° C., and NaH (60% suspension in oil, 175 mg, 4.38 mmol) was added in portions over 5 min. The mixture was stirred at 0° C. for 1 h 40 min, and it was quenched by addition of water and acidified with 2N HCl. The mixture was diluted with CH2Cl2 and washed with brine. The organic fraction was separated, dried over Na2SO4, concentrated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with 0→50% ethyl acetate in hexane to give 5-cyclohex-1-enyl-3-[(trans-4-methoxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (857 mg, 83%). 1H NMR (DMSO-d6, 400 MHz): δ [ppm] 13.1-13.0 (bs, 1H), 6.96 (s, 1H), 6.41 (s, 1H), 4.31-4.24 (m, 1H), 3.12 (s, 3H), 2.90-2.84 (m, 1H), 2.42-2.20 (m, 2H), 2.15 (m, 2H), 1.98-1.78 (m, 4H), 1.68-1.64 (m, 2H), 1.58-1.35 (m, 8H), 1.21-1.02 (m, 5H), 0.87-0.77 (m, 1H), 0.72 (d, J=6.5 Hz, 3H), 0.63-0.46 (m, 2H)

後処理

  1. customit was quenched by addition of water
  2. additionThe mixture was diluted with CH2Cl2
  3. washwashed with brine
  4. customThe organic fraction was separated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel eluting with 0→50% ethyl acetate in hexane

出典と根拠

ORDレコード
ord-16d34539c6924f01971d6c50c32654a6
出典データセット
uspto-grants-2012_04
特許番号
US08158675B2

反応ノート

読み込み中…