Trifluoroacetic acid → 2-(4-Aminophenyl)-6-benzyloxy-3-[3-methoxy-4-(1-pyrrolidinylmethyl)benzyl]benzo[b]thiophene

HRID 1595926ノート

反応式

HRID 1595926 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]([C:17]2[C:18]3[CH:40]=[CH:39][C:38]([O:41][CH2:42][C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)=[CH:37][C:19]=3[S:20][C:21]=2[C:22]2[CH:27]=[CH:26][C:25]([N:28]([Si](C)(C)C)[Si](C)(C)C)=[CH:24][CH:23]=2)=O)[CH:6]=[CH:7][C:8]=1[CH2:9][N:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C1COCC1.ClCCl>[NH2:28][C:25]1[CH:24]=[CH:23][C:22]([C:21]2[S:20][C:19]3[CH:37]=[C:38]([O:41][CH2:42][C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)[CH:39]=[CH:40][C:18]=3[C:17]=2[CH2:15][C:5]2[CH:6]=[CH:7][C:8]([CH2:9][N:10]3[CH2:14][CH2:13][CH2:12][CH2:11]3)=[C:3]([O:2][CH3:1])[CH:4]=2)=[CH:27][CH:26]=1

参加物

7

反応物 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 21226445Aluminium lithium hydrideHCID 224627436-Benzyloxy-2-[4-[bis(trimethylsilyl)amino]phenyl]-benzo[b]thiophen-3-yl 3-methoxy-4-[(1-pyrrolidinyl)methyl]-phenyl ketone

生成物 1

HCID 155495242-(4-Aminophenyl)-6-benzyloxy-3-[3-methoxy-4-(1-pyrrolidinylmethyl)benzyl]benzo[b]thiophene収率 94.1%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

6-Benzyloxy-2-[4-[bis(trimethylsilyl)amino]phenyl]benzo[b]thiophen-3-yl 3-methoxy-4-[(1-pyrrolidinyl)methyl]phenyl ketone (0.73 g) was dissolved in THF (10 mL), cooled to 0° C. in an ice bath before treated with lithium aluminum hydride (110 mg) at 0° C. for 1 h, then quenched with water(1 mL) and sodium hydroxide (1.0 M, 1 mL). Stirring continued for 30 min. The reaction mixture was diluted with brine(30 mL) and extracted with dichloromethane (20 mL×3). The combined organic layers were dried with sodium sulfate and concentrated in vacuo to give the crude alcohol. This material was dissolved in dichloromethane (15 mL), treated with triethylsilane (1.5 mL) and trifluroacetic acid (1.5 mL) sequentially, allowed to stir at ambient temperature for 1.5 h, and concentrated under reduced pressure. The residue was extracted with dichloromethane (20 mL×3) from saturated aqueous sodium bicarbonate (30 mL). The combined organic layers were dried with sodium sulfate and concentrated. Chromatography with Et3N:MeOH:EtOAc (5:5:90) afforded the title compound as a yellow foam (0.53 g).

後処理

  1. customquenched with water(1 mL) and sodium hydroxide (1.0 M, 1 mL)
  2. additionThe reaction mixture was diluted with brine(30 mL)
  3. extractionextracted with dichloromethane (20 mL×3)
  4. dry with materialThe combined organic layers were dried with sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give the crude alcohol
  7. stirringto stir at ambient temperature for 1.5 h
  8. concentrationconcentrated under reduced pressure
  9. extractionThe residue was extracted with dichloromethane (20 mL×3) from saturated aqueous sodium bicarbonate (30 mL)
  10. dry with materialThe combined organic layers were dried with sodium sulfate
  11. concentrationconcentrated

出典と根拠

ORDレコード
ord-53aba11820af4a42b632c6bb3f1c2c74
出典データセット
uspto-grants-2001_09
特許番号
US06288105B1

反応ノート

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