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(4-Amino-5-chloro-2,3-dihydrobenzofuran-7-yl)(1H-imidazol-1-yl)methanone → (+/-)-1,1-Dimethylethyl cis-4-[[[(4-amino-5-chloro-2,3-dihydro-7-benzofuranyl)carbonyl]amino]methyl]-3-hydroxy-1-piperidinecarboxylate

HRID 988122
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 988122
[NH2:1][CH2:2][C@H:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][C@H:4]1[OH:16].[NH2:17][C:18]1[C:23]2[CH2:24][CH2:25][O:26][C:22]=2[C:21]([C:27](N2C=CN=C2)=[O:28])=[CH:20][C:19]=1[Cl:34]>C(#N)C>[NH2:17][C:18]1[C:23]2[CH2:24][CH2:25][O:26][C:22]=2[C:21]([C:27]([NH:1][CH2:2][C@H:3]2[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:13])([CH3:15])[CH3:14])=[O:10])[CH2:5][C@H:4]2[OH:16])=[O:28])=[CH:20][C:19]=1[Cl:34]
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Komponenten

4

Edukt 2

HCID 22662740(4-Amino-5-chloro-2,3-dihydrobenzofuran-7-yl)(1H-imidazol-1-yl)methanoneHCID 57983247Tert-butyl (3s,4r)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate

Produkt 1

HCID 131724101(+/-)-1,1-Dimethylethyl cis-4-[[[(4-amino-5-chloro-2,3-dihydro-7-benzofuranyl)carbonyl]amino]methyl]-3-hydroxy-1-piperidinecarboxylateAusbeute 78 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342
Acetonitrile
Lösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A mixture of intermediate (1-f) (0.09 mol) and intermediate (3-c) (0.087 mol) in ACN (600 ml) was stirred and refluxed for 1 hour. The reaction mixture was cooled to 0° C., and the solvent was evaporated. The residue was partitioned between DCM and water. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 97/3). The pure fractions were collected and the solvent was evaporated. The residue was crystallized from ACN. The precipitate was filtered off and dried), yielding 28.7 g (78%) of (±)-1,1-dimethylethyl cis-4-[[[(4-amino-5-chloro-2,3-dihydro-7-benzofuranyl)carbonyl]amino]methyl]-3-hydroxy-1-piperidinecarboxylate (interm. 4. mp. 218° C.).

Aufarbeitung

  1. temperaturerefluxed for 1 hour
  2. customthe solvent was evaporated
  3. customThe residue was partitioned between DCM and water
  4. customThe organic layer was separated
  5. customdried
  6. filtrationfiltered
  7. customthe solvent was evaporated
  8. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 97/3)
  9. customThe pure fractions were collected
  10. customthe solvent was evaporated
  11. customThe residue was crystallized from ACN
  12. filtrationThe precipitate was filtered off
  13. customdried),

Quellen und Nachweise

ORD-Eintrag
ord-4d6e5ddb45fd4cde94ff6b00b3ec3b93
Quelldatensatz
uspto-grants-2003_10
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US06635643B2

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