Cesium carbonate → Tert-butyl 4-(2-chloro-5-fluorophenoxy)piperidine-1-carboxylate

HRID 1093559Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1093559
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[OH:9].C(=O)([O-])[O-].[Cs+].[Cs+].[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26](OS(C)(=O)=O)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]>CN(C=O)C.O>[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([O:9][C:3]2[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=2[Cl:1])[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 27245222-Chloro-5-fluorophenolHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine

Produkt 1

HCID 16732588Tert-butyl 4-(2-chloro-5-fluorophenoxy)piperidine-1-carboxylateAusbeute 65,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a stirred solution of 2-chloro-5-fluorophenol (6 g, 0.0413 mole) in DMF (20 mL) was added cesium carbonate (26.89 g, 0.00827 mole) followed by 4-methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (11.54 g, 0.04137 mole). The reaction mixture was heated at 80° C. for overnight. The mixture was then diluted with water and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with brine solution, dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by column chromatography using silica gel 230-400 mesh (2% ethyl acetate in hexane) to afford 8.9 g (65%) of 4-(2-chloro-5-fluoro-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester. LCMS: 330.12 (M+1)+, 100%. A solution of 4-(2-chloro-5-fluoro-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester (8.9 g, 0.027 mole) in ethyl acetate.HCl (10 mL) was stirred at ambient temperature for 2 hours. The reaction mixture was then concentrated under reduced pressure and the resulting residue was washed with ether to afford 6.54 g (92%) of. LCMS: 230.07 (M+1)+, 100%, 1H NMR (DMSO-d6): δ 9.6-9.1 (bs, 2H), 7.55-7.45 (t, 1H), 7.35-7.2 (d, 1H), 6.9-6.8 (t, 1H), 4.9-4.7 (s, 1H), 3.26-3.0 (s, 4H), 2.2-2.06 (s, 2H), 2.0-1.8 (s, 2H).

Aufarbeitung

  1. extractionthe product was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with brine solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-798b932608cc45ff99752619b0f6a1ed
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08129376B2

Notizen zur Reaktion

Wird geladen…