1-[2-(4-Bromophenoxy)ethyl]piperidine → (+)-1-[3-Hydroxy-6-[4-(2-piperidin-1-yl-ethoxy)phenyl]-6h-benzo[c]chromen-8-yl]-ethanone

HRID 1359148Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1359148
Br[C:2]1[CH:16]=[CH:15][C:5]([O:6][CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.C([Li])CCC.C[O:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]3[CH:38]=[CH:37][C:36]([C:39]4([CH3:44])OCC[O:40]4)=[CH:35][C:29]=3[C:30](=O)[O:31]2)=[CH:26][CH:25]=1.[Li]>C1COCC1.O>[OH:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]3[CH:38]=[CH:37][C:36]([C:39](=[O:40])[CH3:44])=[CH:35][C:29]=3[CH:30]([C:2]3[CH:16]=[CH:15][C:5]([O:6][CH2:7][CH2:8][N:9]4[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]4)=[CH:4][CH:3]=3)[O:31]2)=[CH:26][CH:25]=1

Komponenten

7

Edukt 4

HCID 8671951-[2-(4-Bromophenoxy)ethyl]piperidine2×HCID 3028194LithiumHCID 113244043-Methoxy-8-(2-methyl-[1,3]-dioxolan-2-yl)-benzo[c]chromen-6-oneHCID 178418339Butyllithium

Produkt 1

HCID 11374158(+)-1-[3-Hydroxy-6-[4-(2-piperidin-1-yl-ethoxy)phenyl]-6h-benzo[c]chromen-8-yl]-ethanoneAusbeute 48 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

1-[2-(4-bromo-phenoxy)-ethyl]-piperidine (0.76 g, 2.7 mmol) from Step F was dissolved in THF (15 ml) under Ar and cooled to −78° C. n-Butyl lithium (10.0 M, 0.26 ml, 2.6 mmol) was added and the mixture was stirred at −78° C. for 1 hour. The compound from Step E (1.11 g, 3.56 mmol) was dissolved in THF (35 ml) under Ar and cooled to −78° C. to which the freshly prepared lithium salt of 1-(2-(4-bromo-phenoxy)-ethyl)-piperidine was transferred via a cannula. The reaction was stirred for 2 h. Water (150 ml) was added and the reaction extracted three times with ethyl acetate (150 ml). After removing the solvent the crude product was chromatographed on silica gel with 7% CH3OH/CH2Cl2 to yield 0.56 g (48%) of the title compound. 1H-NMR (400 MHz, CDCl3) δH 1.44 (2H, m, NCH2CH2CH2), 1.59 (4H, m, NCH2CH2CH2) 1.61 (3H, s, CH3), 2.25 (4H, m, NCH2CH2CH2), 2.83 (2H, m, NCH2CH2O), 3.78 (2H, m, OCH2), 3.85 (3H, s, OCH3), 4.01 (2H, m, OCH2), 4.18 (2H, m, NCH2CH2O), 6.69 (1H, s, ArH), 6.73 (1H, d, ArH), 6.96 (2H, d, ArH), 7.17 (1H, s, ArH), 7.56 (1H, m, ArH), 7.60 (2H, d, ArH), 7.76 (2H, m, ArH).

Aufarbeitung

  1. additionwas added
  2. stirringThe reaction was stirred for 2 h
  3. extractionthe reaction extracted three times with ethyl acetate (150 ml)
  4. customAfter removing the solvent the crude product
  5. customwas chromatographed on silica gel with 7% CH3OH/CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-12f7047f8ecf414fa7f70b8e77c55f5a
Quelldatensatz
uspto-grants-2003_07
Patentnummer
US06599921B2

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