Methyl iodide → (2R)-3-(Benzo[b]thiophen-3-yl)-2-(tert-butoxycarbonyl-methylamino)propionic acid

HRID 495812ノート

反応式

HRID 495812 の反応式
[S:1]1[CH:5]=[C:4]([CH2:6][C@@H:7]([NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:8]([OH:10])=[O:9])[C:3]2[CH:19]=[CH:20][CH:21]=[CH:22][C:2]1=2.CI.[H-].[Na+].[C:27](OCC)(=O)C>O1CCCC1.O>[S:1]1[CH:5]=[C:4]([CH2:6][C@@H:7]([N:11]([C:12]([O:14][C:15]([CH3:17])([CH3:18])[CH3:16])=[O:13])[CH3:27])[C:8]([OH:10])=[O:9])[C:3]2[CH:19]=[CH:20][CH:21]=[CH:22][C:2]1=2

参加物

7

反応物 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 7020915(R)-3-(Benzo[b]thiophen-3-yl)-2-((tert-butoxycarbonyl)amino)propanoic acid

生成物 1

HCID 54409748(2R)-3-(Benzo[b]thiophen-3-yl)-2-(tert-butoxycarbonyl-methylamino)propionic acid

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

(2R)-3-(Benzo[b]thiophen-3-yl)-2-tert-butoxycarbonylamino-propionic acid (2.65 g; 8.25 mmol) was dissolved in dry tetrahydrofuran. Methyl iodide was added and the reaction mixture was cooled to 0° C. Sodium hydride (60% in mineral oil, 0.80 g, 24.8 mmol) was added. The reaction mixture was stirred for 48 hours at room temperature. Ethyl acetate (25 mL) and water (10 mL) were added dropwise. The solvent was removed in vacuo and the residue was dissolved in ether (15 mL) and water (15 mL). The organic phase was washed with an aqueous solution of sodium hydrogen carbonate (saturated; 20 mL). To the aqueous phase was added citric acid (5%) until pH 3 and extracted with ethyl acetate (4×20 mL). The combined is organic phases were washed with water (2×30 mL), an aqueous solution of sodium thiosulfate (5%; 30 mL) and water (30 mL) and dried (magnesium sulfate). The solvent was removed in vacuo and the residue was dissolved in ether (10 mL). Dicyclohexylamine (5 mL) was added. The precipitated crystals were filtered off, washed with ether (2×10 mL) and dissolved in water (30 mL). An aqueous solution of sodium hydrogen sulfate (10%; 20 mL) and ethyl acetate (40 mL) were added. The aqueous phase was extrated with ethylacetate (4×30 mL) and dried (magnesium sulfate). The solvent was removed in vacuo to afford 3.75 g of (2R)-3-(benzo[b]thiophen-3-yl)-2-(tert-butoxycarbonyl methylamino)propionic acid.

後処理

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in ether (15 mL)
  3. washThe organic phase was washed with an aqueous solution of sodium hydrogen carbonate (saturated; 20 mL)
  4. additionTo the aqueous phase was added citric acid (5%) until pH 3
  5. extractionextracted with ethyl acetate (4×20 mL)
  6. washwere washed with water (2×30 mL)
  7. dry with materialan aqueous solution of sodium thiosulfate (5%; 30 mL) and water (30 mL) and dried (magnesium sulfate)
  8. customThe solvent was removed in vacuo
  9. dissolutionthe residue was dissolved in ether (10 mL)
  10. additionDicyclohexylamine (5 mL) was added
  11. filtrationThe precipitated crystals were filtered off
  12. washwashed with ether (2×10 mL)
  13. dissolutiondissolved in water (30 mL)
  14. additionAn aqueous solution of sodium hydrogen sulfate (10%; 20 mL) and ethyl acetate (40 mL) were added
  15. dry with materialdried (magnesium sulfate)
  16. customThe solvent was removed in vacuo

出典と根拠

ORDレコード
ord-8205ee2571054d40b0a9e691931afc95
出典データセット
uspto-grants-2005_09
特許番号
US06939880B2

反応ノート

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