Ethyl Acetate → 5-Chloro-6'-(cyclohexyloxy)-3,3'-bipyridin-2-amine

HRID 1747952Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1747952
Br[C:2]1[C:3]([NH2:9])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH:10]1([O:16][C:17]2[N:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.C(=O)([O-])[O-].[Na+].[Na+].CCOC(C)=O>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>[Cl:8][C:6]1[CH:7]=[C:2]([C:20]2[CH:21]=[N:22][C:17]([O:16][CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]3)=[CH:18][CH:19]=2)[C:3]([NH2:9])=[N:4][CH:5]=1

Komponenten

8

Edukt 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 27639713-Bromo-5-chloropyridin-2-amineHCID 66747855B-[6-(cyclohexyloxy)-3-pyridinyl]Boronic acid

Produkt 1

HCID 667489945-Chloro-6'-(cyclohexyloxy)-3,3'-bipyridin-2-amineAusbeute 90,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel2×HCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

n-Butyllithium (1.6 M in hexane) (20.5 mL) was dropwised to a mixture of 5-bromo-2-(cyclohexyloxy)pyridine (7.00 g) and THF (dry) (75 mL) at −78° C. and the mixture was stirred at the same temperature under nitrogen for 40 min. Triisopropyl borate (7.71 g) was dropwised to the mixture at −78° C. and the mixture was stirred at the same temperature for 5 min. Then the mixture was warmed up to room temperature and stirred for additional 30 min. The mixture was poured into 1N NaOH aq. (75 mL)/water (120 mL) and stirred for 1 hr. The organic layer was separated and the aqueous phase was washed with Et2O (100 mL×2) and neutralized by 1N HCl aq. The mixture was extracted with EtOAc, dried over anhydrous sodium sulfate and concentrated in vacuo to give [6-(cyclohexyloxy)pyridin-3-yl]boronic acid (5.15 g) as pale yellow solid. Tetrakis(triphenylphosphine)palladium(0) (107 mg) was added to a suspension of 3-bromo-5-chloropyridin-2-amine (640 mg), [6-(cyclohexyloxy)pyridin-3-yl]boronic acid (750 mg) and sodium carbonate (654 mg) in DME (15 mL) and water (3 mL) and the mixture was stirred at 100° C. under nitrogen for 2.5 hr. Water and EtOAc were added and the organic layer was separated, washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with EtOAc in hexane) to give the title compound (846 mg) as colorless gum.

Aufarbeitung

  1. customthe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (silica gel, eluted with EtOAc in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-62d2f6e934854ff9b14d780feae6b3a6
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09150591B2

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