3-Acetamidophthalic Anhydride → 3-(4-Acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid

HRID 1694247

反応式

HRID 1694247 の反応式
[NH2:1][CH:2]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH:14]([F:16])[F:15])=[C:9]([O:17][CH2:18][CH:19]2[CH2:21][CH2:20]2)[CH:8]=1)[CH2:3][C:4]([OH:6])=[O:5].[C:22]([NH:25][C:26]1[CH:36]=[CH:35][CH:34]=[C:28]2[C:29]([O:31][C:32](=O)[C:27]=12)=[O:30])(=[O:24])[CH3:23].C([O-])(=O)C.[Na+]>C(O)(=O)C>[C:22]([NH:25][C:26]1[CH:36]=[CH:35][CH:34]=[C:28]2[C:27]=1[C:32](=[O:31])[N:1]([CH:2]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH:14]([F:16])[F:15])=[C:9]([O:17][CH2:18][CH:19]3[CH2:21][CH2:20]3)[CH:8]=1)[CH2:3][C:4]([OH:6])=[O:5])[C:29]2=[O:30])(=[O:24])[CH3:23]

参加物

5

反応物 3

HCID 2261213-Acetamidophthalic AnhydrideHCID 517045Sodium AcetateHCID 21082338HCID 21082338、化合物

生成物 1

HCID 98483373-(4-Acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid収率 147.4%

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒

実験手順

To a solution of 3-amino-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid (500 mg, 1.0 mmol) in acetic acid (10 ml) was added 3-acetamido-phthalic anhydride (390 mg, 1.9 mmol) and sodium acetate (160 mg, 1.9 mmol). The mixture was heated at reflux temperature overnight. The solvent was removed in vacuo. The resulted oil was extracted with ethyl acetate (50 ml) and water (30 ml). The organic layer was washed with water (30 ml×4), brine (30 ml) and dried over magnesium sulfate. The solvent was removed in vacuo and the resulted oil was slurried with ether for 2 hours. The suspension was filtered to give 3-(4-acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid as a white solid (720 mg, 85%). 1HNMR (CDCl3): 0.35-0.39 (m, 2H), 0.64-0.68 (m, 2H), 1.15-1.36 (m, 1H), 2.27 (s, 3H), 3.24 (dd, J=5.8, 17 Hz, 1H), 3.82 (dd, J=10, 17 Hz, 1H), 3.88 (d, J=8.3 Hz, 2H), 5.70 (dd, J=5.8, 10 Hz, 1H), 6.59 (t, JH-F=75 Hz, 1H), 7.06-7.14 (m, 3H), 7.48 (d, J=7.3 Hz, 1H), 7.65 (t, J=7.5 Hz, 1H), 8.76 (d, J=8.3 Hz, 1H), 9.47 (s, 1H).

後処理

  1. temperatureThe mixture was heated
  2. temperatureat reflux temperature overnight
  3. customThe solvent was removed in vacuo
  4. extractionThe resulted oil was extracted with ethyl acetate (50 ml) and water (30 ml)
  5. washThe organic layer was washed with water (30 ml×4), brine (30 ml)
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. filtrationThe suspension was filtered

出典と根拠

ORDレコード
ord-42014ae5b8db495aa87f3dbf02d88659
出典データセット
uspto-grants-2012_04
特許番号
US08158672B2

関連ノート

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