Dimethylformamide → Methyl (2S)-3-[3-bromo-4-(2-tert-butyl-1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)phenyl]-2-[(tert-butoxycarbonyl)amino]propanoate

HRID 724658ノート

反応式

HRID 724658 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([CH2:9][C@H:10]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:11]([O:13][CH3:14])=[O:12])[CH:5]=[CH:6][C:7]=1I.[C:23]([N:27]1[C:31](=[O:32])[CH:30]=[CH:29][S:28]1(=[O:34])=[O:33])([CH3:26])([CH3:25])[CH3:24].C(N(CC)CC)C.CN(C=O)C>CCCC[N+](CCCC)(CCCC)CCCC.[Cl-].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH2:9][C@H:10]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:11]([O:13][CH3:14])=[O:12])[CH:5]=[CH:6][C:7]=1[C:29]1[S:28](=[O:33])(=[O:34])[N:27]([C:23]([CH3:25])([CH3:24])[CH3:26])[C:31](=[O:32])[CH:30]=1

参加物

7

反応物 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 111168162-Tert-butyl-2,3-dihydro-1lambda6,2-thiazole-1,1,3-trioneHCID 11569273Methyl (2S)-3-(3-bromo-4-iodophenyl)-2-[(tert-butoxycarbonyl)amino]-propanoate

生成物 1

HCID 11562959Methyl (2S)-3-[3-bromo-4-(2-tert-butyl-1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)phenyl]-2-[(tert-butoxycarbonyl)amino]propanoate収率 52.2%

試薬・触媒・溶媒 2

HCID 70681Tetrabutylammonium Chloride触媒HCID 167845palladium(II) acetate触媒

反応条件

温度
70 °C

実験手順

Methyl (2S)-3-(3-bromo-4-iodophenyl)-2-[(tert-butoxycarbonyl)amino]-propanoate (2.35 g, 4.85 mmol), 2-tert-butylisothiazol-3(2H)-one 1,1-dioxide (1.61 g, 8.49 mmol), palladium acetate (218 mg, 0.971 mmol), tetra-N-butylammonium chloride (1.35 g, 4.85 mmol), and then triethylamine (2.03 mL, 14.6 mmol) were dissolved in DMF (40.0 mL, 0.516 mmol). The solution was degassed and then stirred with heating at 70° C. under nitrogen for 120 minutes. LCMS indicated an absence of starting material. The solution was diluted with ethyl acetate (150 mL) and washed with water (150 mL) and aqueous hydrochloric acid solution (1.0 N, 150 mL). The organic phase was filtered through celite with ethyl acetate washing. The organic solution was dried over sodium sulfate, concentrated in vacuo, and then purified by silica gel chromatography (slow gradient, 10–25% ethyl acetate/hexanes) to afford product as a yellow solid (1.38 g, 52%). 1H NMR (500 MHz, CD3OD): δ 7.80 (d, J=8.2 Hz, 1H), 7.55 (s, 1H), 7.23 (d, J=8.2 Hz, 1H), 6.89 (s, 1H), 5.08–5.05 (m, 1H), 4.62–4.59 (m, 1H), 3.76 (s, 3H), 3.23–3.20 (m, 1H), 3.06–3.02 (m, 1H), 1.79 (s, 9H), 1.43 (s, 9H). LCMS found for C22H29BrN2O7SNa (M+Na)+: m/z=567.

後処理

  1. customThe solution was degassed
  2. additionThe solution was diluted with ethyl acetate (150 mL)
  3. washwashed with water (150 mL) and aqueous hydrochloric acid solution (1.0 N, 150 mL)
  4. filtrationThe organic phase was filtered through celite with ethyl acetate washing
  5. dry with materialThe organic solution was dried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel chromatography (slow gradient, 10–25% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-9bb60d4cc80f463dac47105e6f0f0b05
出典データセット
uspto-grants-2006_11
特許番号
US07141596B2

反応ノート

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