1,2-Dimethoxyethane → 6-(3-(Tert-butoxycarbonyl)phenyl)-2-chloronicotinic acid

HRID 2284350

Reaktionsgleichung

Reaktionsgleichung von HRID 2284350
[Cl:1][C:2]1[N:10]=[C:9](Cl)[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:12]([O:16][C:17]([C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][CH:24]=1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C(=O)([O-])[O-].[K+].[K+].COCCOC>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:12]([O:16][C:17]([C:19]1[CH:24]=[C:23]([C:9]2[CH:8]=[CH:7][C:3]([C:4]([OH:6])=[O:5])=[C:2]([Cl:1])[N:10]=2)[CH:22]=[CH:21][CH:20]=1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Komponenten

7

Edukt 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 8540472,6-Dichloronicotinic acidHCID 2773299(3-((Tert-butoxy)carbonyl)phenyl)boronic acid

Produkt 1

HCID 866909876-(3-(Tert-butoxycarbonyl)phenyl)-2-chloronicotinic acidAusbeute 67,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel2×

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

2,6-Dichloronicotinic acid (1.20 g, 6.25 mmol), 3-(tert-butoxycarbonyl)benzene boronic acid (2.08 g, 9.10 mmol), potassium carbonate (2.60 g, 18.8 mmol), tetrakis(triphenylphosphine)palladium (0.72 g, 0.62 mmol), degassed 1,2-dimethoxyethane (30 mL) and water (0.5 mL) were combined under an argon atmosphere and the mixture heated at 90° C. overnight. The reaction mixture was then cooled to room temperature, diluted with water (100 mL) and extracted with ethyl acetate (2×150 mL). The aqueous layer was acidified to pH 3-4 using 2N HCl solution and extracted with ethyl acetate (2×200 mL). The combined organic portions were dried over anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography (silica gel, 20% methanol/dichloromethane) and the product containing fractions concentrated to give a solid, which was triturated with 2:1 heptane/ethyl acetate to give pure 6-(3-(tert-butoxycarbonyl)phenyl)-2-chloronicotinic acid (1.4 g, 67%) as an off-white foam. 1H NMR (400 MHz, CD3OD) δ ppm 8.64 (s, 1H), 8.34 (d, 1H), 8.29 (d, 1H), 8.04 (d, 1H), 7.95 (d, 1H), 7.59 (t, 1H), 1.60 (s, 9H); m/z 334 [M+H].

Aufarbeitung

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. extractionextracted with ethyl acetate (2×150 mL)
  3. extractionextracted with ethyl acetate (2×200 mL)
  4. dry with materialThe combined organic portions were dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (silica gel, 20% methanol/dichloromethane)
  7. additionthe product containing fractions
  8. concentrationconcentrated
  9. customto give a solid, which
  10. customwas triturated with 2:1 heptane/ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-aef9144150944c1099a549ed8aecfcfd
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09145416B2

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