Succinic anhydride → 4-[4-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-indol-1-yl]-4-oxo-butyric acid

HRID 551512ノート

反応式

HRID 551512 の反応式
[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]3[CH:25]=[CH:24][CH:23]=[C:22]4[C:18]=3[CH:19]=[CH:20][NH:21]4)=[CH:11][CH:10]=2)=[C:4]([O:26][CH3:27])[CH:3]=1.C(N(CC)CC)C.[C:35]1(=[O:41])[O:40][C:38](=[O:39])[CH2:37][CH2:36]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>CN(C)C=O>[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]3[CH:25]=[CH:24][CH:23]=[C:22]4[C:18]=3[CH:19]=[CH:20][N:21]4[C:35](=[O:41])[CH2:36][CH2:37][C:38]([OH:40])=[O:39])=[CH:11][CH:10]=2)=[C:4]([O:26][CH3:27])[CH:3]=1

参加物

6

反応物 4

HCID 7922Succinic anhydrideHCID 8471TriethylamineHCID 2733832Lithium HexamethyldisilazideHCID 529397424-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-1H-indole

生成物 1

HCID 529397434-[4-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-indol-1-yl]-4-oxo-butyric acid収率 34.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

To 4-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-1H-indole (37 mg, 0.10 mmol, 1 eq.) was added dimethylformamide (1 mL), triethylamine (0.154 ml, 1.1 mmol, 10 eq.) and succinic anhydride (30 mg, 0.3 mmol, 3 eq.) the reaction was stir at 80° C. for 8 hr and allowed to cool to room temperature. Lithium bis(trimethylsilyl)amide (1 M in THF, 1.2 mL, 1.2 mmol, 12 eq) was added and the reaction was allowed to proceed at room temperature for 24 hr. The reaction was purified by HPLC with a 30-100% acetonitrile in water gradient and dried from dichloromethane/hexanes mixture to yield 4-[4-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-indol-1-yl]-4-oxo-butyric acid as a white solid (16 mg, 34%). LC-MS (ES) calculated for C26H21F2NO5, 465.1; found m/z 466 [M+H]+.

後処理

  1. temperatureto cool to room temperature
  2. waitto proceed at room temperature for 24 hr
  3. customThe reaction was purified by HPLC with a 30-100% acetonitrile in water gradient
  4. dry with materialdried from dichloromethane/hexanes mixture

出典と根拠

ORDレコード
ord-fefe8bf6b8084406a2dff607098cf017
出典データセット
uspto-grants-2011_05
特許番号
US07947728B1

反応ノート

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