Acetic Acid → 4-[4-(4-[2-[(2R)-2-Hydroxy-2-(4-hydroxy-3-methanesulfonylamino-phenyl)-ethylamino]-ethyl)-phenylamino)-piperidin-1-yl]-benzoic acid ethyl ester

HRID 1281625

Reaktionsgleichung

Reaktionsgleichung von HRID 1281625
CO[CH:3](OC)[C:4]1[CH:27]=[CH:26][C:7]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:25]=[CH:24]C(C(OCC)=O)=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[CH:6][CH:5]=1.[I-].[Na+].Cl[Si](Cl)(Cl)C.[C:37](O)(=O)C.[NH2:41][CH2:42][C@@H:43]([C:45]1[CH:46]=[CH:47][C:48]([OH:56])=[C:49]([NH:51][S:52]([CH3:55])(=[O:54])=[O:53])[CH:50]=1)[OH:44].C([BH3-])#N.[Na+].Cl.[C:62]([O:65][CH2:66][CH3:67])(=[O:64])[CH3:63]>C(#N)C.O1CCCC1.CO.ClCCl>[CH2:66]([O:65][C:62](=[O:64])[C:63]1[CH:17]=[CH:16][C:15]([N:12]2[CH2:11][CH2:10][CH:9]([NH:8][C:7]3[CH:6]=[CH:5][C:4]([CH2:3][CH2:37][NH:41][CH2:42][C@H:43]([OH:44])[C:45]4[CH:46]=[CH:47][C:48]([OH:56])=[C:49]([NH:51][S:52]([CH3:55])(=[O:54])=[O:53])[CH:50]=4)=[CH:27][CH:26]=3)[CH2:14][CH2:13]2)=[CH:25][CH:24]=1)[CH3:67]

Komponenten

13

Edukt 8

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 6399TrichloromethylsilaneHCID 8857Ethyl AcetateHCID 5003444Sodium cyanoborohydrideHCID 12047933(R)-N-(5-(2-amino-1-hydroxyethyl)-2-hydroxyphenyl)methanesulfonamideHCID 18173737Ethyl 4-{4-[4-(dimethoxymethyl)anilino]-1-piperidinyl}benzoate

Produkt 1

HCID 699870244-[4-(4-[2-[(2R)-2-Hydroxy-2-(4-hydroxy-3-methanesulfonylamino-phenyl)-ethylamino]-ethyl)-phenylamino)-piperidin-1-yl]-benzoic acid ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 887MethanolLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Ethyl 4-{4-[4-(dimethoxymethyl)anilino]-1-piperidinyl}benzoate (0.63 g, 01.53 mmol) was added to a pre-prepared mixture of sodium iodide (0.572 g, 3.82 mmol) and trichloro(methyl)silane (0.36 mL, 3.07 mmol) in anhydrous acetonitrile. The reaction was stirred at ambient temperature for 3 minutes. Dichloromethane was added and the reaction washed with 10% sodium thiosulfate solution, water and brine. The organic layer was dried with anhydrous magnesium sulfate, filtered and the solvent partially removed in vacuo. The aldehyde solution was used directly and treated with methanol, tetrahydrofuran, acetic acid (0.091 mL, 1.53 mmol), N-{5-[(1R)-2-amino-1-hydroxyethyl]-2-hydroxyphenyl}methanesulfonamide (0.377 g, 0.1.53 mmol) followed by sodium cyanoborohydride (0.105 g, 1.53 mmol). The reaction was stirred at ambient temperature overnight. 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). The hydrochoride salt of the title compound was generated from anhydrous etheral hydrochloric acid in ethyl acetate (0.14 g, 0.221 mmol).

Aufarbeitung

  1. washthe reaction washed with 10% sodium thiosulfate solution, water and brine
  2. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  3. filtrationfiltered
  4. customthe solvent partially removed in vacuo
  5. stirringThe reaction was stirred at ambient temperature overnight
  6. custompurified by flash chromatography on silica gel Merck-60 (eluant: 5:1 chloroform-methanol containing 1% ammonium hydroxide)

Quellen und Nachweise

ORD-Eintrag
ord-1becad67b8f3465f831458974e05296f
Quelldatensatz
uspto-grants-2002_09
Patentnummer
US06451814B1

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