Ethyl Acetate → methyl (R)-1-(2-phenoxyethyl)piperidine-2-carboxylate

HRID 1854229Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1854229
[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][C@@H:2]1[C:7]([O:9][CH3:10])=[O:8].C([O-])([O-])=O.[K+].[K+].Br[CH2:18][CH2:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CCOC(C)=O>CN(C=O)C>[O:20]([CH2:19][CH2:18][N:1]1[CH2:6][CH2:5][CH2:4][CH2:3][C@@H:2]1[C:7]([O:9][CH3:10])=[O:8])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Komponenten

6

Edukt 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 68526Benzene, (2-bromoethoxy)-HCID 7408456methyl (R)-piperidine-2-carboxylate

Produkt 1

HCID 52294458methyl (R)-1-(2-phenoxyethyl)piperidine-2-carboxylateAusbeute 64 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Dissolve methyl (R)-piperidine-2-carboxylate (5.00 g, 34.9 mmol) in DMF (87 mL) and treat with K2CO3 (14.48 g, 104.8 mmol) and β-bromophenetole (7.16 g, 34.9 mmol). Stir the mixture overnight at 100° C. Cool the mixture to room temperature and add EtOAc (250 mL). Wash the organic phase with water (4×100 mL) and saturated aqueous NaCl (100 mL). Dry the organic phase over K2CO3, filter to remove the solids, and concentrate the filtrate under reduced pressure to furnish a yellow oil. Subject this crude material to flash chromatography on silica gel eluting with a gradient of 20% to 100% EtOAc/hexanes. Concentrate the fractions containing the desired product under reduced pressure to furnish the title compound as a colorless oil in ca. 90% purity by 1H NMR analysis (6.50 g, 64% yield). Mass spectrum (m/z) 264 (M+H)+. 1H NMR (400 MHz, CDCl3): δ 7.27 (dd, J=8.5, 7.3 Hz, 2H), 6.93 (t, J=7.3 Hz, 1H), 6.88 (d, J=8.8 Hz, 2H), 4.10 (app t, J=6.1 Hz, 2H), 3.72 (s, 3H), 3.29 (dd, J=8.4, 4.0 Hz, 1H), 3.14 (app dt, J=11.3, 6.4 Hz, 1H), 2.95 (app dt, J=13.7, 6.1 Hz, 1H), 2.89 (app dt, J=13.7, 6.1 Hz, 1H), 2.42 (ddd, J=11.6, 7.9, 3.7 Hz, 1H), 1.90-1.82 (m, 1H), 1.79 (app td, J=8.9, 3.8 Hz, 1H), 1.67-1.59 (m, 3H), 1.39 (app td, J=8.8, 4.0 Hz, 1H).

Aufarbeitung

  1. temperatureCool the mixture to room temperature
  2. washWash the organic phase with water (4×100 mL) and saturated aqueous NaCl (100 mL)
  3. dry with materialDry the organic phase over K2CO3
  4. filtrationfilter
  5. customto remove the solids
  6. concentrationconcentrate the filtrate under reduced pressure
  7. customto furnish a yellow oil
  8. concentrationConcentrate the fractions
  9. additioncontaining the desired product under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-052fa8a0c94140559628cb25e13268e8
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08962659B2

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