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Sodium cyanoborohydride → (1S,2S)-2-[(E)-3-(4-Acetylamino-4-phenyl-piperidin-1-yl)-propenyl]-1-(3,4-dichloro-phenyl)-cyclopropanecarboxylic acid (4-fluoro-benzyl)-methyl-amide

HRID 1172223
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1172223
[C:1]1([C:7]2([NH:13][C:14](=[O:16])[CH3:15])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:17][C:18]1[CH:43]=[CH:42][C:21]([CH2:22][N:23]([CH3:41])[C:24]([C@@:26]2([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([Cl:40])[CH:34]=3)[CH2:28][C@H:27]2/[CH:29]=[CH:30]/[CH:31]=O)=[O:25])=[CH:20][CH:19]=1.C([BH3-])#N.[Na+]>C(O)C>[F:17][C:18]1[CH:43]=[CH:42][C:21]([CH2:22][N:23]([CH3:41])[C:24]([C@@:26]2([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([Cl:40])[CH:34]=3)[CH2:28][C@H:27]2/[CH:29]=[CH:30]/[CH2:31][N:10]2[CH2:11][CH2:12][C:7]([NH:13][C:14](=[O:16])[CH3:15])([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:8][CH2:9]2)=[O:25])=[CH:20][CH:19]=1
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Komponenten

5

Edukt 3

HCID 5003444Sodium cyanoborohydrideHCID 15886675N-(4-Phenylpiperidin-4-yl)acetamideHCID 86609590(1S,2S)-1-(3,4-Dichloro-phenyl)-2-((E)-3-oxo-propenyl)-cyclopropanecarboxylic acid (4-fluoro-benzyl)-methyl-amide

Produkt 1

HCID 67423469(1S,2S)-2-[(E)-3-(4-Acetylamino-4-phenyl-piperidin-1-yl)-propenyl]-1-(3,4-dichloro-phenyl)-cyclopropanecarboxylic acid (4-fluoro-benzyl)-methyl-amide

Reagenzien, Katalysatoren, Lösungsmittel

1
HCID 702EthanolLösungsmittel2×

Versuchsvorschrift

N-(4-Phenyl-piperidin-4-yl)-acetamide (140 mg, 0.64 mmol) dissolved in ethanol (3 ml) is added to (1S,2S)-1-(3,4-Dichloro-phenyl)-2-((E)-3-oxo-propenyl)-cyclopropanecarboxylic acid (4-fluoro-benzyl)-methyl-amide dissolved in ethanol (5 ml) followed by dropwise addition of sodium cyanoborohydride (1.0M in THF, 1.97 ml, 1.97 mmol) at 0° C. After complete addition the mixture is kept at ambient temperature for 2 hours. The reaction is quenched by addition of sodium bicarbonate (3 ml, sat.) and the ethanol is removed by means of evaporation. Ethyl acetate (30 ml) is added to the remanence. The organic fraction is washed successively with sodium bicarbonate (10 ml, sat.) and brine (10 ml, sat.), dried (MgSO4) and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with ethyl acetate:ethanol:triethylamine (95:0:5)-(90:5:5) to furnish the title compound as an oil. Yield 81 mg (27%). LC/MS (m/z) 610.3 (M+H+).

Aufarbeitung

  1. additionAfter complete addition the mixture
  2. customThe reaction is quenched by addition of sodium bicarbonate (3 ml, sat.)
  3. customthe ethanol is removed by means of evaporation
  4. additionEthyl acetate (30 ml) is added to the remanence
  5. washThe organic fraction is washed successively with sodium bicarbonate (10 ml, sat.) and brine (10 ml, sat.)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by silica gel chromatography
  9. washeluting with ethyl acetate:ethanol:triethylamine (95:0:5)-(90:5:5)

Quellen und Nachweise

ORD-Eintrag
ord-b7c10c9369f745fb96e72181082299de
Quelldatensatz
uspto-grants-2010_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07834008B2

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