Potassium Carbonate → 4-[4-(2,2-Difluoro-cyclopropylmethoxy)-phenyl]-piperidine hydrochloride

HRID 1617316Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1617316
[F:1][C:2]1([F:11])[CH2:4][CH:3]1[CH2:5][O:6]S(C)(=O)=O.C(OC([N:19]1[CH2:24][CH2:23][CH:22]([C:25]2[CH:30]=[CH:29][C:28](O)=[CH:27][CH:26]=2)[CH2:21][CH2:20]1)=O)(C)(C)C.C([O-])([O-])=O.[K+].[K+].[Cl-:38].[Na+].O>CN(C=O)C>[ClH:38].[F:1][C:2]1([F:11])[CH2:4][CH:3]1[CH2:5][O:6][C:28]1[CH:27]=[CH:26][C:25]([CH:22]2[CH2:21][CH2:20][NH:19][CH2:24][CH2:23]2)=[CH:30][CH:29]=1

Komponenten

6

Edukt 4

HCID 11430Potassium CarbonateHCID 19381871tert-Butyl 4-(4-hydroxyphenyl)piperidine-1-carboxylateHCID 57417360Sodium chloride; waterHCID 58198163Cyclopropanemethanol, 2,2-difluoro-, 1-methanesulfonate

Produkt 1

HCID 896473844-[4-(2,2-Difluoro-cyclopropylmethoxy)-phenyl]-piperidine hydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

4.48 g (19.2 mmol, 80%) Methanesulfonic acid 2,2-difluoro-cyclopropylmethyl ester are added to 5.93 g (19.2 mmol, 90%) 4-(4-hydroxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester and 5.36 g (38.5 mmol) K2CO3 in 60 mL DMF. Stirring is continued for 12 h at 50° C. under inert gas atmosphere. After that time, brine (50 mL) is added and the mixture is extracted with EtOAc (3×50 mL). The organic layer is separated, washed with brine, dried over sodium sulphate and the solvent is removed by evaporation. The residue is purified by column chromatography (silica gel; gradient PE:EtOAc 20:1→10:1). The residue is taken up in 20 mL DCM and 100 mL 4N HCl in EtOAc are added dropwise at 0° C. The mixture is stirred for 12 h at rt. After that time, the solvent is removed in vacuo to yield the desired product.

Aufarbeitung

  1. extractionthe mixture is extracted with EtOAc (3×50 mL)
  2. customThe organic layer is separated
  3. washwashed with brine
  4. dry with materialdried over sodium sulphate
  5. customthe solvent is removed by evaporation
  6. customThe residue is purified by column chromatography (silica gel; gradient PE:EtOAc 20:1→10:1)
  7. addition100 mL 4N HCl in EtOAc are added dropwise at 0° C
  8. stirringThe mixture is stirred for 12 h at rt
  9. customAfter that time, the solvent is removed in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-af5bca9b524d4374936ef868da62e6db
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765959B2

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