Reaktion #483236

Reaktionsgleichung

sodium cyanoborohydride

acetic acid

N-{5-[(1R)-2-amino-1-hydroxyethyl]-2-hydroxyphenyl}methanesulfonamide

methanol

sodium iodide

Methyl (2S)-1-({4-[4-(2,2-dimethoxyethyl)anilino]-1-piperidinyl)carbonyl)-2-pyrrolidinecarboxylate

trichloro(methyl)silane

→

title compound

1-[[4-[[4-[2-[[(2R)-2-Hydroxy-2-[4-hydroxy[(methylsulfonyl)amino]phenyl]ethyl]amino]ethyl]phenyl]amino]-1-piperidinyl]carbonyl]-L-proline, methyl ester

Lösungsmittel

Dichloromethane

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   Waschenthe reaction washed with 10% sodium thiosulfate solution, water and brine
2. 2
   TrocknenThe organic layer was dried over anhydrous magnesium sulfate
3. 3
   Filtrationfiltered
4. 4
   Sonstigethe solvent partially removed in vacuo
5. 5
   workup.STIRRINGThe reaction was stirred at ambient temperature for 24 hours
6. 6
   Sonstigepurified by flash chromatography on silica gel Merck-60 (eluant: 5:1 chloroform-methanol containing 1% ammonium hydroxide)

Vorschrift

Methyl (2S)-1-({4-[4-(2,2-dimethoxyethyl)anilino]-1-piperidinyl)carbonyl)-2-pyrrolidinecarboxylate (1.0 g, 2.38 mmol) was added to a pre-prepared mixture of sodium iodide (0.837 g, 5.58 mmol) and trichloro(methyl)silane (0.525 mL, 4.46 mmol) in anhydrous acetonitrile. The reaction was stirred at ambient temperature for 10 minutes. Dichloromethane was added and the reaction washed with 10% sodium thiosulfate solution, water and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent partially removed in vacuo. The aldehyde solution was used directly and treated with methanol, acetic acid (0.146 mL, 2.43 mmol), N-{5-[(1R)-2-amino-1-hydroxyethyl]-2-hydroxyphenyl}methanesulfonamide (0.55 g, 2.23 mmol) followed by sodium cyanoborohydride (0.154 g, 2.24 mmol). The reaction was stirred at ambient temperature for 24 hours. The reaction was taken to dryness in vacuo, adsorbed onto silica and purified by flash chromatography on silica gel Merck-60 (eluant: 5:1 chloroform-methanol containing 1% ammonium hydroxide) to yield the title compound (0.05 g, 0.083 mmol).

Quelle