Triethylamine → tert-butyl 4-{[(3R,4R)-4-{[(4-chlorophenyl)carbonyl](methyl)amino}-3-(3,4-dichlorophenyl)piperidin-1-yl]methyl}piperidine-1-carboxylate

HRID 1260969Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1260969
Cl.[Cl:2][C:3]1[CH:26]=[CH:25][C:6]([C:7]([N:9]([C@@H:11]2[CH2:16][CH2:15][NH:14][CH2:13][C@H:12]2[C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=2)[CH3:10])=[O:8])=[CH:5][CH:4]=1.[CH:27]([CH:29]1[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]1)=O.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.O.C(OCC)(=O)C>[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([N:9]([CH3:10])[C@@H:11]2[CH2:16][CH2:15][N:14]([CH2:27][CH:29]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:39])([CH3:41])[CH3:40])=[O:36])[CH2:31][CH2:30]3)[CH2:13][C@H:12]2[C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=2)=[O:8])=[CH:25][CH:26]=1

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 689287034-chloro-N-[(3R,4R)-3-(3,4-dichlorophenyl)piperidin-4-yl]-N-methylbenzamide Monohydrochloride

Produkt 1

HCID 68932507tert-butyl 4-{[(3R,4R)-4-{[(4-chlorophenyl)carbonyl](methyl)amino}-3-(3,4-dichlorophenyl)piperidin-1-yl]methyl}piperidine-1-carboxylateAusbeute 58,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 176Acetic AcidLösungsmittelHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a mixture of 4-chloro-N-[(3R,4R)-3-(3,4-dichlorophenyl)piperidin-4-yl]-N-methylbenzamide monohydrochloride (300 mg) obtained in Example 137a, tert-butyl 4-formylpiperidine-1-carboxylate (735 mg) and triethylamine (105 μL) in acetic acid (0.69 mL)-ethyl acetate (10 mL) was added sodium triacetoxyborohydride (731 mg), and the mixture was stirred at room temperature for 14 hr. The reaction mixture was poured into water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with water and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 60→90% ethyl acetate/hexane, and then 0→30% methanol/ethyl acetate) to give the title compound (242 mg, 58%) as a white powder.

Aufarbeitung

  1. extractionthe resultant product was extracted with ethyl acetate
  2. washThe organic layer was washed with water
  3. customdried
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (solvent gradient

Quellen und Nachweise

ORD-Eintrag
ord-b51869cea2f04d91a71776afa2102b87
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08470816B2

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