Methanol → tert-butyl 2-[(3R*,4S*)-1-{[2-chloro-6-(trifluoromethyl)phenyl]methyl}-3-{[1-(2-fluoropentyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetate

HRID 445996Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 445996
C([N:8]1[CH2:12][C@@H:11]([CH3:13])[C@@:10]([CH2:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])([C:14](=[O:28])[NH:15][CH:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH:23]([F:27])[CH2:24][CH2:25][CH3:26])[CH2:18][CH2:17]2)[CH2:9]1)C1C=CC=CC=1.CO.Br[CH2:40][C:41]1[C:46]([C:47]([F:50])([F:49])[F:48])=[CH:45][CH:44]=[CH:43][C:42]=1[Cl:51].C(=O)([O-])[O-].[K+].[K+]>[OH-].[Pd+2].[OH-].O.CN(C)C=O>[Cl:51][C:42]1[CH:43]=[CH:44][CH:45]=[C:46]([C:47]([F:50])([F:49])[F:48])[C:41]=1[CH2:40][N:8]1[CH2:12][C@@H:11]([CH3:13])[C@@:10]([CH2:29][C:30]([O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:31])([C:14](=[O:28])[NH:15][CH:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH:23]([F:27])[CH2:24][CH2:25][CH3:26])[CH2:18][CH2:17]2)[CH2:9]1

Komponenten

8

Edukt 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 177506812-(Bromomethyl)-1-chloro-3-(trifluoromethyl)benzeneHCID 71293809tert-butyl 2-[(3R*,4S*)-1-benzyl-3-{[1-(2-fluoropentyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetate

Produkt 1

HCID 71293836tert-butyl 2-[(3R*,4S*)-1-{[2-chloro-6-(trifluoromethyl)phenyl]methyl}-3-{[1-(2-fluoropentyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetateAusbeute 78,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9942167Palladium hydroxideKatalysator2×HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

A mixture of the chiral form of tert-butyl 2-[(3R*,4S*)-1-benzyl-3-{[1-(2-fluoropentyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetate obtained in Example 1k (161 mg, 0.32 mmol), 20% palladium hydroxide (135 mg) and methanol (5 ml) was stirred at mom temperature for 15 hours under a hydrogen atmosphere. The atmosphere in the reaction vessel was replaced with nitrogen, 20% palladium hydroxide was filtered off, and the solvent was distilled off. 2-(Bromomethyl)-1-chloro-3-(trifluoromethyl)benzene (159 mg, 0.581 mmol), potassium carbonate (97 mg, 0.702 mmol) and N,N-dimethylformamide (2 ml) were added to the resulting residue, which was heated at 45° C. for three hours and 15 minutes. Water was added to the reaction mixture, which was extracted with ethyl acetate twice. The organic layer was washed with a saturated aqueous ammonium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography (NH silica gel, elution solvent: ethyl acetate/heptane) to give the title compound (153 mg, yield 78.9%).

Aufarbeitung

  1. filtrationwas filtered off
  2. distillationthe solvent was distilled off
  3. extractionwas extracted with ethyl acetate twice
  4. washThe organic layer was washed with a saturated aqueous ammonium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off
  7. customThe residue was purified by silica gel column chromatography (NH silica gel, elution solvent: ethyl acetate/heptane)

Quellen und Nachweise

ORD-Eintrag
ord-309f7b5c84c84d4db34407c1ec922b0b
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08476301B2

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