Cesium carbonate → 4-Tert-butyl-2-(2-chloro-4-fluorophenoxy)benzoic acid

HRID 1625199

Reaktionsgleichung

Br[C:2]1[CH:10]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[Cl:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[OH:23].C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1>[C:11]([C:9]1[CH:8]=[CH:7][C:3]([C:4]([OH:6])=[O:5])=[C:2]([O:23][C:17]2[CH:18]=[CH:19][C:20]([F:22])=[CH:21][C:16]=2[Cl:15])[CH:10]=1)([CH3:14])([CH3:13])[CH3:12]

Komponenten

Reaktionsbedingungen

Temperatur: 120 °C

Versuchsvorschrift

In a pressure-vessel, a stirring mixture of 2-bromo-4-tert-butylbenzoic acid (1.00 g, 3.89 mmol) and 2-chloro-4-fluorophenol (860 mg, 620 μL, 5.87 mmol) in toluene (20 mL) was added Cs2CO3 (2.53 g, 7.78 mmol) followed by copper(I) triflate benzene complex (98 mg, 0.19 mmol). The sealed vessel was heated to 120° C. for 16 h. After cooling to room temperature, the reaction mixture was partitioned between 50 mL EtOAc and 50 mL H2O. The aqueous layer was acidified using 2.0 N HCl(aq) and re-extracted with EtOAc. The combined organic solution was dried over Na2SO4, filtered, and concentrated. The residue was purified via silica gel chromatography using 0-3% MeOH/CH2Cl2 to give the product, 4-tert-butyl-2-(2-chloro-4-fluorophenoxy)benzoic acid as a white solid (907 mg, 2.81 mmol) in 72% yield. LC/MS: m/z 323.2 (M+H) at 1.99 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Aufarbeitung

temperatureAfter cooling to room temperature
customthe reaction mixture was partitioned between 50 mL EtOAc and 50 mL H2O
extractionre-extracted with EtOAc
dry with materialThe combined organic solution was dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified via silica gel chromatography

Quellen und Nachweise

ORD-Eintrag: ord-729cbca1987243dba6b471d9c68653b3
Quelldatensatz: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08779197B2

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