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

HRID 1928706
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HRID 1928706 반응식
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
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참가 물질

5

반응물 3

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

생성물 1

HCID 25067786Hexanamide, 3-amino-N-cyclopropyl-2-hydroxy-, hydrochloride (1:1), (2S,3S)-수율 16.8%

시약·촉매·용매 1

HCID 3776Isopropanol용매2회

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온도
60 °C

실험 절차

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).

후처리

  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.

출처 및 근거

ORD 기록
ord-94ffa2c6a2a048ae8449ccb5f6df3dc8
출처 데이터셋
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08183413B2

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