Borohydride → benzyl (5R)-5-{[(tert-butylamino)carbothioyl]amino}-6-hydroxyhexylcarbamate

HRID 47730

Reaktionsgleichung

Reaktionsgleichung von HRID 47730
[Cl-].[Li+].[BH4-].[Na+].[CH2:5]([O:12][C:13]([NH:15][CH2:16][CH2:17][CH2:18][CH2:19][C@@H:20]([NH:26][C:27]([NH:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[S:28])[C:21](OCC)=[O:22])=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[BH4-]>C(O)C.O1CCCC1.ClCCl.C(OCC)(=O)C>[C:30]([NH:29][C:27]([NH:26][C@@H:20]([CH2:21][OH:22])[CH2:19][CH2:18][CH2:17][CH2:16][NH:15][C:13](=[O:14])[O:12][CH2:5][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)=[S:28])([CH3:33])([CH3:32])[CH3:31]

Komponenten

8

Edukt 4

HCID 28123BorohydrideHCID 433294Lithium ChlorideHCID 4311764Sodium borohydrideHCID 86584428ethyl (2R)-6-{[(benzyloxy)carbonyl]amino}-2-{[(tert-butylamino)carbothioyl]amino}hexanoate

Produkt 1

HCID 86584427benzyl (5R)-5-{[(tert-butylamino)carbothioyl]amino}-6-hydroxyhexylcarbamateAusbeute 60,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 702EthanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 21226138Dichloromethane ethylacetateLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

1.78 g of lithium chloride and then 1.6 g of sodium borohydride are added, under an inert atmosphere, to a stirred solution of 12.7 g of ethyl (2R)-6-{[(benzyloxy)-carbonyl]amino}-2-{[(tert-butylamino)carbothioyl]-amino}hexanoate in 130 cm3 of ethanol and 65 cm3 of tetrahydrofuran, cooled to between 0° C. and 5° C. After stirring for 16 hours at a temperature in the region of 20° C., a further 0.4 g of borohydride is added and the mixture is maintained at about 80° C. for 4 hours. The reaction medium is filtered and the filter cake is washed with ethanol. The filtrate is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. and the residue obtained is taken up in a dichloromethane/ethyl acetate mixture (85/15 by volume) and left under cold conditions at about 5° C. The crystalline product is spin-filtered and purified by chromatography at atmospheric pressure on a column of silica gel (particle size 40-63μ; mass of silica: 600 g), eluting with a dichloromethane/ethyl acetate mixture (85/15 by volume). The fractions containing the expected product are collected. These fractions are combined and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. 6.9 g of benzyl (5R)-5-{[(tert-butylamino)carbothioyl]amino}-6-hydroxyhexylcarbamate are obtained in the form of a colorless oil. (αD20=+24.0±0.8 at a concentration of 0.5% in methanol).

Aufarbeitung

  1. temperaturecooled to between 0° C. and 5° C
  2. temperaturethe mixture is maintained at about 80° C. for 4 hours
  3. filtrationThe reaction medium is filtered
  4. washthe filter cake is washed with ethanol
  5. concentrationThe filtrate is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C.
  6. customthe residue obtained
  7. waitleft under cold conditions at about 5° C
  8. filtrationThe crystalline product is spin-filtered
  9. custompurified by chromatography at atmospheric pressure on a column of silica gel (particle size 40-63μ; mass of silica: 600 g)
  10. washeluting with a dichloromethane/ethyl acetate mixture (85/15 by volume)
  11. additionThe fractions containing the expected product
  12. customare collected
  13. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C

Quellen und Nachweise

ORD-Eintrag
ord-ec536c627bf4400c83228e481c75e4d0
Quelldatensatz
uspto-grants-2004_03
Patentnummer
US06699895B2

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