Sodium hydride → {9-[(3-Fluorophenyl)methyl]-2-methyl-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl ester

HRID 567234ノート

反応式

HRID 567234 の反応式
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([CH2:10][N:11]2[C:23]3[CH:22]=[C:21]([CH3:24])[CH:20]=[C:19]([OH:25])[C:18]=3[C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][C:16]=3[C:26](=[O:28])[NH2:27])[CH:7]=[CH:8][CH:9]=1.Br[CH2:30][C:31]([O:33][CH3:34])=[O:32]>CN(C=O)C.C1COCC1.C(OCC)(=O)C>[F:3][C:4]1[CH:5]=[C:6]([CH2:10][N:11]2[C:23]3[CH:22]=[C:21]([CH3:24])[CH:20]=[C:19]([O:25][CH2:30][C:31]([O:33][CH3:34])=[O:32])[C:18]=3[C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][C:16]=3[C:26](=[O:28])[NH2:27])[CH:7]=[CH:8][CH:9]=1

参加物

7

反応物 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 227400919-[(3-Fluorophenyl)methyl]-2-methyl-4-hydroxy-5-carbamoyl carbazole

生成物 1

HCID 86756257{9-[(3-Fluorophenyl)methyl]-2-methyl-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl ester収率 78%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

60% Sodium hydride in mineral oil (25.9 mg, 0.65 mM) was added to a solution of 9-[(3-fluorophenyl)methyl]-2-methyl-4-hydroxy-5-carbamoyl carbazole (181 mg, 0.52 mM) in 18 mL DMF and 3.9 ml THF. After 10 minutes, methyl bromoacetate (66 μl, 0.70 mM) was added and the resultant mixture stirred at room temperature for 1.25 hours. The mixture was diluted with ethyl acetate and washed with H2O. The aqueous layer was extracted with ethyl acetate. The combined organic layers were extracted with saturated brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel (elution with methylene chloride/acetone gradient) to afford 170 mg (78%) of the {9-[(3-fluorophenyl)methyl]-2-methyl-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl ester. 1H NMR (DMSO-d6) δ 7.55 (d, 1H, J=8 Hz), 7.5 (bs, 1H), 7.4-7.25 (m, 2H), 7.2 (bs, 1H), 7.05 (m, 3H), 6.95 (d, J=8 Hz, 1H), 6.9 (d, J=8 Hz), 6.45 (s, 1H), 5.65 (s, 2H), 4.9 (s, 2H), 3.75 (s, 3H), 2.4 (s, 3H). MS (FD) m/e 404, 421.

後処理

  1. washwashed with H2O
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. extractionThe combined organic layers were extracted with saturated brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (elution with methylene chloride/acetone gradient)

出典と根拠

ORDレコード
ord-3f9c4a86966b4395ae8d9179bd93f771
出典データセット
uspto-grants-2001_01
特許番号
US06177440B1

反応ノート

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