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Ethyl Acetate → Hexanamide, 3-amino-N-cyclopropyl-2-hydroxy-, hydrochloride (1:1), (2S,3S)-

HRID 1928706
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1928706
C(OCC)(=O)C.[CH:7]1([NH:10][C:11](=[O:26])[C@@H:12]([OH:25])[C@@H:13]([NH:17]C(OC(C)(C)C)=O)[CH2:14][CH2:15][CH3:16])[CH2:9][CH2:8]1.[ClH:27].C(O)(C)C>C(O)(C)C>[ClH:27].[CH:7]1([NH:10][C:11](=[O:26])[C@@H:12]([OH:25])[C@@H:13]([NH2:17])[CH2:14][CH2:15][CH3:16])[CH2:9][CH2:8]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

5

Edukt 3

HCID 8857Ethyl AcetateHCID 21912024Isopropanol hydrochlorideHCID 68950941tert-Butyl ((2S,3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-yl)carbamate

Produkt 1

HCID 25067786Hexanamide, 3-amino-N-cyclopropyl-2-hydroxy-, hydrochloride (1:1), (2S,3S)-Ausbeute 16,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776
Isopropanol
Lösungsmittel
2×

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

The ethyl acetate solution of (2S,3S)—N-cyclopropyl-3-(tert-butoxycarbonyl)amino-2-hydroxyhexanoic acid amide (92.2 g, 10.8 wt. %) obtained in the above Example 2 was used. The solvent was changed from ethyl acetate to isopropyl alcohol, thereby to prepare an isopropyl alcohol solution of (2S,3S)—N-cyclopropyl-3-(tert-butoxycarbonyl)amino-2-hydroxyhexanoic acid amide (69.63 g). The solution was heated up to 60° C., and 10.5 wt % hydrogen chloride/isopropyl alcohol solution (18.2 g) was dropwise added, taking 1 hour. After stirred for 8 hours, the reaction solution was cooled down to 0° C. at a constant rate, taking about 6 hours. The slurry had no solid aggregation therein, and had good flowability. The precipitated crystals were collected by filtration under reduced pressure, using a kiriyama funnel (diameter 6 cm, filter pore size 4 μm). At the time, the filterability was good, and the time taken for separation of the crystals from the mother liquid was about 30 seconds. The obtained wet crystals were washed with hexane/isopropyl alcohol=1/1 solution (30 mL). Next, the washed wet crystals were dried in vacuum at 60° C., to obtain (2S,3S)—N-cyclopropyl-3-amino-2-hydroxyhexanoic acid amide hydrochloride (7.06 g, isolation yield: 90 mol %, chemical purity: 100.0 area %, optical purity: 100% ee).

Aufarbeitung

  1. temperaturethe reaction solution was cooled down to 0° C. at a constant rate
  2. waittaking about 6 hours
  3. filtrationThe precipitated crystals were collected by filtration under reduced pressure
  4. filtration(diameter 6 cm, filter pore size 4 μm)
  5. customthe time taken for separation of the crystals from the mother liquid
  6. waitwas about 30 seconds
  7. washThe obtained wet crystals were washed with hexane/isopropyl alcohol=1/1 solution (30 mL)
  8. customNext, the washed wet crystals were dried in vacuum at 60° C.

Quellen und Nachweise

ORD-Eintrag
ord-94ffa2c6a2a048ae8449ccb5f6df3dc8
Quelldatensatz
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08183413B2

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