Sodium borohydride → (2R,3R)-3-hydroxy-8-methyl-2-(4-methylphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one

HRID 1033480

Reaktionsgleichung

Reaktionsgleichung von HRID 1033480
N[C@@H](C(O)=O)C(C)(C)C.[BH4-].[Na+].[CH3:12][C:13]1[CH:32]=[CH:31][C:16]2[NH:17][C:18](=[O:30])[C:19](=[O:29])[CH:20]([C:22]3[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=3)[S:21][C:15]=2[CH:14]=1.C(O)(=O)C.O1CCCC1>O1CCCC1>[OH:29][C@@H:19]1[C:18](=[O:30])[NH:17][C:16]2[CH:31]=[CH:32][C:13]([CH3:12])=[CH:14][C:15]=2[S:21][C@@H:20]1[C:22]1[CH:23]=[CH:24][C:25]([CH3:28])=[CH:26][CH:27]=1

Komponenten

6

Edukt 4

HCID 4311764Sodium borohydrideHCID 6950340D-tert-leucineHCID 190261378-methyl-2-(4-methyl-phenyl)-1,5-benzothiazepine-3,4(2H,5H)-dioneHCID 23444217Acetic acid tetrahydrofuran

Produkt 1

HCID 10566075(2R,3R)-3-hydroxy-8-methyl-2-(4-methylphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-oneAusbeute 80,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-15 °C

Versuchsvorschrift

A mixture of D-tert-leucine (721 mg), sodium borohydride (189 mg) and tetrahydrofuran (50 ml) is refluxed under nitrogen atmosphere for three hours. The mixture is cooled to -15° C., and thereto is added a solution of 8-methyl-2-(4-methylphenyl)-1,5-benzothiazepine-3,4(2H, 5H)-dione (991 mg) in tetrahydrofuran (3 ml). Each 0.38 ml of 25% acetic acid/tetrahydrofuran solution (1.67 mmole as acetic acid) is added thereto at 25 minutes, and 2 hours 10 minutes after the beginning of the reaction, and the reaction solution is stirred at the same temperature for 20 hours. The mixture is evaporated under reduced pressure to remove the solvent, and to the residue is added 1N hydrochloric acid (70 ml). The precipitated crystal is collected by filtration, washed with water, and dried. The collected crystal is suspended in isopropyl alcohol (12 ml), and the mixture is heated with stirring at 80° C. for three hours. The mixture is cooled to 5° C., and allowed to stand for five hours. The precipitated crystal is collected by filtration, washed with cold isopropyl alcohol, and dried to give (2R,3R)-3-hydroxy-8-methyl-2-(4-methylphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one (804 mg).

Aufarbeitung

  1. temperatureis refluxed under nitrogen atmosphere for three hours
  2. custom2 hours 10 minutes after the beginning of the reaction
  3. customThe mixture is evaporated under reduced pressure
  4. customto remove the solvent
  5. additionto the residue is added 1N hydrochloric acid (70 ml)
  6. filtrationThe precipitated crystal is collected by filtration
  7. washwashed with water
  8. customdried
  9. temperaturethe mixture is heated
  10. stirringwith stirring at 80° C. for three hours
  11. temperatureThe mixture is cooled to 5° C.
  12. waitto stand for five hours
  13. filtrationThe precipitated crystal is collected by filtration
  14. washwashed with cold isopropyl alcohol
  15. customdried

Quellen und Nachweise

ORD-Eintrag
ord-9275edf4827441378485aeff29604116
Quelldatensatz
uspto-grants-1994_05
Patentnummer
US05310904

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