4-Chlorobenzenesulfonyl chloride → (2S)-2-(4-chloro-benzenesulfonylamino)-5,5,5-trifluoro-3-(2,2,2-trifluoroethyl)pentanoic acid methyl ester

HRID 1454079

Reaktionsgleichung

Reaktionsgleichung von HRID 1454079
[CH3:1][O:2][C:3](=[O:17])[C@@H:4]([NH2:16])[CH:5]([CH2:11][C:12]([F:15])([F:14])[F:13])[CH2:6][C:7]([F:10])([F:9])[F:8].[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([S:25](Cl)(=[O:27])=[O:26])=[CH:21][CH:20]=1>>[CH3:1][O:2][C:3](=[O:17])[C@@H:4]([NH:16][S:25]([C:22]1[CH:23]=[CH:24][C:19]([Cl:18])=[CH:20][CH:21]=1)(=[O:27])=[O:26])[CH:5]([CH2:6][C:7]([F:9])([F:10])[F:8])[CH2:11][C:12]([F:15])([F:14])[F:13]

Komponenten

3

Edukt 2

HCID 73984-Chlorobenzenesulfonyl chlorideHCID 25112112(2S)-2-amino-5,5,5-trifluoro-3-(2,2,2-trifluoroethyl)-pentanoic acid methyl ester

Produkt 1

HCID 25112113(2S)-2-(4-chloro-benzenesulfonylamino)-5,5,5-trifluoro-3-(2,2,2-trifluoroethyl)pentanoic acid methyl ester

Versuchsvorschrift

In another embodiment, a method for preparing 4-chloro-N-[(1S)-4,4,4-trifluoro-1-hydroxymethyl-2-(2,2,2-trifluoroethyl)-butyl]benzenesulfonamide is provided and includes (a) reacting 1,1,1-trifluoro-3-iodopropane with triphenylphosphine to form (3,3,3-trifluoropropyl)-triphenylphosphonium iodide; (b) reacting (3,3,3-trifluoropropyl)-triphenylphosphonium iodide and a base at a temperature of −70° C. to 25° C.; (c) reacting the product of step (b) with ethylchloroformate at a temperature below about −20° C. to form 4,4,4-trifluoro-2-(triphenyl-λ5-phosphanylidene)-butyric acid ester; (d) isolating 4,4,4-trifluoro-2-(triphenyl-λ5-phosphanylidene)-butyric acid ester by hydrocarbon trituration; (e) reacting dehydrated trifluoroacetaldehyde, which is free of acidic impurities, and 4,4,4-trifluoro-2-(triphenyl-λ5-phosphanylidene)-butyric acid ester to form 4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)-but-2-enoic acid ester; (f) hydrogenating 4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)-but-2-enoic acid ester to form 4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)-butyric acid ester; (g) reacting 4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)-butyric acid ester with N,O-dimethylhydroxylamine hydrochloride to form 4,4,4-trifluoro-N-methoxy-N-methyl-2-(2,2,2-trifluoroethyl)-butyramide; (h) reacting 4,4,4-trifluoro-N-methoxy-N-methyl-2-(2,2,2-trifluoroethyl)-butyramide with a first reducing agent to form 4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)-butyraldehyde; (i) reacting 4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)-butyraldehyde, a titanium alkoxide, and (S)-(+)-p-toluenesulfinamide to form N-methyl-N-[(1S)-4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)-butylidene]benzenesulfinamide; (j) cyanating N-methyl-N-[(1S)-4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)-butylidene]benzenesulfinamide to form N-methyl-benzenesulfinic acid [(1S)-1-cyano-4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)-butyl]amide; (k) reacting N-methyl-benzenesulfinic acid [(1S)-1-cyano-4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)-butyl]amide with an aqueous acid; (l) reacting the product of step (k) with an alcohol in the presence of an acid to form (2S)-2-amino-5,5,5-trifluoro-3-(2,2,2-trifluoroethyl)-pentanoic acid methyl ester; (m) reacting (2S)-2-amino-5,5,5-trifluoro-3-(2,2,2-trifluoroethyl)-pentanoic acid methyl ester with 4-chlorobenzenesulfonyl chloride to form (2S)-2-(4-chloro-benzenesulfonylamino)-5,5,5-trifluoro-3-(2,2,2-trifluoroethyl)-pentanoic acid methyl ester; (n) combining (2S)-2-(4-chloro-benzenesulfonylamino)-5,5,5-trifluoro-3-(2,2,2-trifluoroethyl)-pentanoic acid methyl ester and a second reducing agent to form 4-chloro-N-[(1S)-4,4,4-trifluoro-1-hydroxymethyl-2-(2,2,2-trifluoroethyl)-butyl]benzenesulfonamide; (o) quenching the product of step (n); and (p) isolating the 4-chloro N-[(1S)-4,4,4-trifluoro-1-hydroxymethyl-2-(2,2,2-trifluoroethyl)-butyl]benzenesulfonamide.

Quellen und Nachweise

ORD-Eintrag
ord-bb27882534ea496499aa09ed196ac1db
Quelldatensatz
uspto-grants-2009_01
Patentnummer
US07476762B2

Verknüpfte Notizen

Wird geladen…