Lithium Hydroxide → 1-((3-Fluoro-4-(5-(phenylmethyl)-1H-indol-2-yl)phenyl)methyl)-3-azetidinecarboxylic acid

HRID 2075221ノート

反応式

HRID 2075221 の反応式
[CH2:1]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12]([C:17]1[CH:31]=[CH:30][C:20]([CH2:21][N:22]3[CH2:25][CH:24]([C:26]([O:28]C)=[O:27])[CH2:23]3)=[CH:19][C:18]=1[F:32])=[CH:11]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Li+]>C1COCC1.O.CC(O)=O>[F:32][C:18]1[CH:19]=[C:20]([CH2:21][N:22]2[CH2:23][CH:24]([C:26]([OH:28])=[O:27])[CH2:25]2)[CH:30]=[CH:31][C:17]=1[C:12]1[NH:13][C:14]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[CH:16][CH:15]=2

参加物

6

反応物 2

HCID 3939Lithium HydroxideHCID 58415313Methyl 1-(4-(5-benzyl-1H-indol-2-yl)-3-fluorobenzyl)azetidine-3-carboxylate

生成物 1

HCID 248503621-((3-Fluoro-4-(5-(phenylmethyl)-1H-indol-2-yl)phenyl)methyl)-3-azetidinecarboxylic acid

試薬・触媒・溶媒 3

HCID 176Acetic Acid溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of methyl 1-(4-(5-benzyl-1H-indol-2-yl)-3-fluorobenzyl)azetidine-3-carboxylate (0.090 g, 0.21 mmol) in THF (1.0 mL) and water (1.0 mL) was added lithium hydroxide (0.025 g, 1.1 mmol). The solution was stirred at rt for 1 h, or until starting material was no longer observed by LCMS. The solvent was removed under reduced pressure, and 0.5M phosphate buffer (3.0 mL, pH 6.0) was added (pH was ca. 9-10). The mixture was acidified with 1N HCl to pH 6.0 and sonicated for 5 min. The aqueous solution was extracted with EtOAc (3×15 mL), and the separated organic extracts were dried over MgSO4, filtered and concentrated to afford a brown oil. The oil was dissolved in AcOH (3.0 mL), and the excess AcOH was removed under reduced pressure. Ether (15 mL) was added, and the resulting precipitate was collected by filtration. The brown solids were washed with water (10 mL) and chloroform (15 mL) to afford title compound as a yellow solid [hS1P1 EC50=1336 nM]. MS (ESI) m/z: Calculated: 414.1; Observed: 415.1 (M++1).

後処理

  1. customThe solvent was removed under reduced pressure, and 0.5M phosphate buffer (3.0 mL, pH 6.0)
  2. additionwas added (pH was ca. 9-10)
  3. customsonicated for 5 min
  4. extractionThe aqueous solution was extracted with EtOAc (3×15 mL)
  5. dry with materialthe separated organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford a brown oil
  9. customthe excess AcOH was removed under reduced pressure
  10. additionEther (15 mL) was added
  11. filtrationthe resulting precipitate was collected by filtration
  12. washThe brown solids were washed with water (10 mL) and chloroform (15 mL)

出典と根拠

ORDレコード
ord-9fa4219f33494ef488dd2118aa506943
出典データセット
uspto-grants-2011_04
特許番号
US07919519B2

反応ノート

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