Hydrochloric Acid → 2-[2-Amino-2-(3-bromo-phenyl)-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid methyl ester

HRID 81565

Reaktionsgleichung

[CH3:1][O:2][C:3](=[O:24])[C:4]([O:10][CH2:11][C:12]([N:21]=[N+]=[N-])([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Br:20])[CH:15]=1)[CH3:13])([CH3:9])[C:5]([F:8])([F:7])[F:6].[In].Cl.C([O-])([O-])=O.[K+].[K+]>C1COCC1.O>[CH3:1][O:2][C:3](=[O:24])[C:4]([O:10][CH2:11][C:12]([NH2:21])([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Br:20])[CH:15]=1)[CH3:13])([CH3:9])[C:5]([F:8])([F:7])[F:6]

Komponenten

Reaktionsbedingungen

Temperatur: 25 °C

Versuchsvorschrift

To a solution of the 2-[2-azido-2-(3-bromo-phenyl)-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid methyl ester (4.2 g, 9.22 mmol) in THF-H2O 3:1 (48 ml) was added indium (2.116 g, 18.43 mmol) followed by 4N aqueous HCl over a period of 20 min and stirring for 1 h at 25° C. The reaction mixture was added to a 10% aqueous K2CO3 solution and the product was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered and evaporated. The crude product was purified by flash-chromatography on NEt3 deactivated silica gel (hexane/EtOAc 2:1 to EtOAc) to provide a diastereomeric mixture of the title compound as a yellow oil: TLC (EtOAc): Rf=0.46; HPLC RtH55=0.999 min; 1H NMR (360 MHz, CDCl3): δ 7.73 (s, 1H), 7.47 (d, 1H), 7.41 (d, 1H), 7.24 (t, 1H), 3.84 and 3.83 (s, 3H), 3.59 (s, 2H), 1.61 and 1.59 (s, 3H), 1.52 and 1.51 (s, 3H); ESIMS: 384, 386 [(M+H)+].

Aufarbeitung

extractionthe product was extracted with EtOAc
washThe combined organic layers were washed with brine
dry with materialdried over MgSO4
filtrationfiltered
customevaporated
customThe crude product was purified by flash-chromatography on NEt3 deactivated silica gel (hexane/EtOAc 2:1 to EtOAc)
customto provide

Quellen und Nachweise

ORD-Eintrag: ord-3cb9056988fb4cb18b883481526b6c27
Quelldatensatz: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08846658B2

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