Tetrahydrofuran → 1-[2-[3-(3,4-Dichloro-phenyl)-1-(3,4,5-trimethoxy-benzyl)-pyrrolidin-3-yl]-ethyl]-4-phenyl-piperidine-4-carboxylic acid amide

HRID 400057Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 400057
Cl.[C:2]1([C:8]2([C:14]([NH2:16])=[O:15])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:17][O:18][C:19]1[CH:20]=[C:21]([CH:39]=[C:40]([O:44][CH3:45])[C:41]=1[O:42][CH3:43])[CH2:22][N:23]1[CH2:27][CH2:26][C:25]([C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([Cl:38])[CH:32]=2)([CH2:28][CH:29]=O)[CH2:24]1.C([BH3-])#N.[Na+].O1CCCC1.[OH-].[K+]>CO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].ClCCl.CO.C(OCC)(=O)C.ClCCl>[Cl:38][C:33]1[CH:32]=[C:31]([C:25]2([CH2:28][CH2:29][N:11]3[CH2:10][CH2:9][C:8]([C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)([C:14]([NH2:16])=[O:15])[CH2:13][CH2:12]3)[CH2:26][CH2:27][N:23]([CH2:22][C:21]3[CH:39]=[C:40]([O:44][CH3:45])[C:41]([O:42][CH3:43])=[C:19]([O:18][CH3:17])[CH:20]=3)[CH2:24]2)[CH:36]=[CH:35][C:34]=1[Cl:37]

Komponenten

11

Edukt 5

HCID 8028TetrahydrofuranHCID 14797Potassium HydroxideHCID 30171294-Phenylpiperidine-4-carboxamide monohydrochlorideHCID 5003444Sodium cyanoborohydrideHCID 189450891-(3,4,5-Trimethoxybenzyl)-3-(3,4-dichloro-phenyl)-3-(2-oxo-ethyl)-pyrrolidine

Produkt 1

HCID 539696501-[2-[3-(3,4-Dichloro-phenyl)-1-(3,4,5-trimethoxy-benzyl)-pyrrolidin-3-yl]-ethyl]-4-phenyl-piperidine-4-carboxylic acid amide

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 11026Titanium isopropoxideKatalysatorHCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 21226129Dichloromethane methanolLösungsmittel3×

Versuchsvorschrift

Combine 4-phenyl-piperidine-4-carboxylic acid-amide hydrochloride (0.5 g, 2.1 mmol), 1-(3,4,5-trimethoxybenzyl)-3-(3,4-dichloro-phenyl)-3-(2-oxo-ethyl)-pyrrolidine (0.23 g, 0.53 mmol), and titanium(IV) isopropoxide (0.2 g, 0.7 mmol) in methanol (5 mL). Add a solution of sodium cyanoborohydride in tetrahydrofuran (0.9 mL, 1M, 0.9 mmol). After 18 hours, a precipitate had formed. Filter, rinse with methanol and dichloromethane, and evaporate the filtrate to give a residue. Combine residue with dichloromethane and an aqueous 2M solution of potassium hydroxide. Separate the layers, extract the aqueous layer with dichloromethane, combine the organic layers, dry over MgSO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with ethyl acetate, dichloromethane/methanol/concentrated ammonia (196/4/0.2), dichloromethane/methanol/concentrated ammonia (242/8/0.4), and then dichloromethane/methanol/concentrated ammonia (238/12/0.6) to give the title compound. Elemental Analysis calculated for C34H43 Cl2N3O4.0.4 H2O: C 64.52; H 6.64; N 6.64. Found C 64.15; H 6.33; N 6.67.

Aufarbeitung

  1. customa precipitate had formed
  2. filtrationFilter
  3. washrinse with methanol and dichloromethane
  4. customevaporate the filtrate
  5. customto give a residue
  6. customSeparate the layers
  7. extractionextract the aqueous layer with dichloromethane
  8. dry with materialdry over MgSO4
  9. filtrationfilter
  10. customevaporate in vacuo
  11. customto give a residue

Quellen und Nachweise

ORD-Eintrag
ord-2ee60fa7746c4a8c9a1990218c54c272
Quelldatensatz
uspto-grants-1998_10
Patentnummer
US05824690

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