tert-Butyl 2-(4-bromophenyl)pyrrolidine-1-carboxylate → tert-butyl 2-(4'-((1R,2S)-2-(2,2-dichloroacetamido)-3-fluoro-1-hydroxypropyl)-[1,1'-biphenyl]-4-yl)pyrrolidine-1-carboxylate

HRID 2283173

Reaktionsgleichung

[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[CH:18]=[CH:17][C:16](Br)=[CH:15][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:20][CH:21]([Cl:40])[C:22]([NH:24][C@H:25]([CH2:38][F:39])[C@H:26]([OH:37])[C:27]1[CH:32]=[CH:31][C:30]([Sn](C)(C)C)=[CH:29][CH:28]=1)=[O:23]>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:20][CH:21]([Cl:40])[C:22]([NH:24][C@H:25]([CH2:38][F:39])[C@@H:26]([C:27]1[CH:28]=[CH:29][C:30]([C:16]2[CH:17]=[CH:18][C:13]([CH:9]3[CH2:10][CH2:11][CH2:12][N:8]3[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[CH:14][CH:15]=2)=[CH:31][CH:32]=1)[OH:37])=[O:23]

Komponenten

Reaktionsbedingungen

Temperatur: 80 °C

Versuchsvorschrift

A mixture of commercially available 2-(4-Bromo-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (500 mg, 1.53 mmol), 2,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(trimethylstannyl)phenyl)propan-2-yl)acetamide (679 mg, 1.53 mmol, 1 eq.), P(2-fur)3 (72 mg, 0.31 mmol, 0.2 eq.) and Pd2(dba)3 (142 mg, 0.153 mmol, 0.1 eq.) are dissolved in DMF (8 mL, 0.2 M) and de-oxygenated. The mixture is heated to 80° C. for 16 hours. Reaction is concentrated under vacuum to a syrup and purified on a 24 g silica column eluting from 0-100% EtOAc/heptane) to give the title compound 240 mg.

Aufarbeitung

customReaction
concentrationis concentrated under vacuum to a syrup
custompurified on a 24 g silica column
washeluting from 0-100% EtOAc/heptane)

Quellen und Nachweise

ORD-Eintrag: ord-2d789eb8fb494af0ae133c8b92b68538
Quelldatensatz: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US09145355B2

Verknüpfte Notizen

Wird geladen…