Veratrole → (2,3-Dimethoxyphenyl)(4-pyridinyl)methanol

HRID 51240

Reaktionsgleichung

Reaktionsgleichung von HRID 51240
[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[C@@H:11]([CH:13]1[CH2:18][CH2:17][N:16](CCC2C=CC(F)=CC=2)[CH2:15][CH2:14]1)[OH:12].C1(OC)C(=CC=CC=1)OC.N1C=CC(C=O)=CC=1>>[OH:12][CH:11]([C:13]1[CH:14]=[CH:15][N:16]=[CH:17][CH:18]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[C:8]([O:9][CH3:10])[C:3]=1[O:2][CH3:1]

Komponenten

4

Edukt 3

HCID 7043VeratroleHCID 133894-PyridinecarboxaldehydeHCID 5311271(+)-alpha-(2,3-Dimethoxyphenyl)-1-(2-(4-fluorophenyl)ethyl)-4-piperidinemethanol

Produkt 1

HCID 314742(2,3-Dimethoxyphenyl)(4-pyridinyl)methanol

Versuchsvorschrift

In yet another embodiment, there is provided a process for preparing (R)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (3) comprising the steps of: a) reacting lithiated veratrole with 4-pyridinecarboxaldehyde (9) in the presence of a suitable aprotic solvent to provide 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]pyridine (10); b) subjecting 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]pyridine (10) to catalytic hydrogenation to provide 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]piperidine (11); c) reacting 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]piperidine (11) with a suitable 4-fluorophenylacetylating reagent, in the presence of a suitable base and a suitable solvent to provide 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]-N-2-(4-fluorophen-1-oxo-ethyl)piperidine (20); d) reacting 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]-N-2-(4-fluorophen-1-oxo-ethyl)piperidine (20) with a suitable reducing agent in the presence of a suitable solvent to provide α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (5); e) reacting α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (5) with (2S,3S)-(+)-di-(p-anisoyl)tartaric acid to give a racemic mixture of (R)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol, (2S,3S)-(+)-di-(p-anisoyl)tartaric acid salt (3a) and (S)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol, (2S,3S)-(+)-di-(p-anisoyl)tartaric acid salt (3b); f) separating the (R)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol, (2S,3S)-(+)-di-(p-anisoyl)tartaric acid salt (3b) from the (S)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol, (2S,3S)-(+)-di-(p-anisoyl)tartaric acid salt (3a) by selective crystallization; and g) reacting the (R)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol, (2S,3S)-(+)-di-(p-anisoyl)tartaric acid salt (3a) with a suitable base to give (R)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (3).

Aufarbeitung

  1. customIn yet another embodiment, there is provided a process

Quellen und Nachweise

ORD-Eintrag
ord-c2b0f9b889214d3e82e90d52c745c101
Quelldatensatz
uspto-grants-2004_03
Patentnummer
US06713627B2

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