Hydrochloric Acid → HCID 89656488、化合物

HRID 930914ノート

反応式

HRID 930914 の反応式
[F:1][C:2]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([CH3:14])(=[O:13])=[O:12])=[CH:7][C:6]=1[C:15]1[C:16]2[CH:25]=[C:24]([CH:26]=[O:27])[NH:23][C:17]=2[C:18](=[O:22])[N:19]([CH3:21])[CH:20]=1.[CH3:33][Mg]Br.Cl>O1CCCC1>[F:1][C:2]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([CH3:14])(=[O:12])=[O:13])=[CH:7][C:6]=1[C:15]1[C:16]2[CH:25]=[C:24]([CH:26]([OH:27])[CH3:33])[NH:23][C:17]=2[C:18](=[O:22])[N:19]([CH3:21])[CH:20]=1

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 89657403HCID 89657403、化合物HCID 178418573HCID 178418573、化合物

生成物 1

HCID 89656488HCID 89656488、化合物収率 24.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To a solution of Example 278a (0.20 g, 0.44 mmol) in tetrahydrofuran (6 mL) at 0° C. was added methylmagnesium bromide (1.0 M in tetrahydrofuran, 0.873 mL, 0.873 mmol). The reaction mixture was stirred at 0° C. for one hour, and then 1M aqueous HCl (2 mL) was added. The reaction mixture was concentrated and partitioned between saturated aqueous sodium chloride (10 mL) and ethyl acetate (2×30 mL). The combined organic phase was washed with saturated aqueous sodium chloride (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by preparative thin layer chromatography (silica gel, dichloromethane/methanol, 15/1) to provide the title compound (51 mg, 24% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.83 (s, 1H), 7.96 (d, J=2.4 Hz, 1H), 7.86 (dd, J=2.4, 6.4 Hz, 1H), 7.55-7.50 (m, 1H), 7.42-7.36 (m, 2H), 7.20-7.15 (m, 1H), 6.97 (d, J=8.8 Hz, 1H), 6.15 (d, J=2 Hz, 1H), 5.13 (d, J=5.2 Hz, 1H), 4.80-4.77 (m, 1H), 3.57 (s, 3H), 3.25 (s, 3H), 1.38 (d, J=6.4 Hz, 3H). MS (ESI+) m/z 475.1 (M+1)+.

後処理

  1. concentrationThe reaction mixture was concentrated
  2. custompartitioned between saturated aqueous sodium chloride (10 mL) and ethyl acetate (2×30 mL)
  3. washThe combined organic phase was washed with saturated aqueous sodium chloride (30 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by preparative thin layer chromatography (silica gel, dichloromethane/methanol, 15/1)

出典と根拠

ORDレコード
ord-733b089f79cc44eaa9e091e5303d41fd
出典データセット
uspto-grants-2016_03
特許番号
US09296741B2

反応ノート

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