Cesium carbonate → tert-butyl 4-(5-isopropoxy-2-methyl-4-nitrophenyl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 1850898Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1850898
[CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([O:11][CH:12]([CH3:14])[CH3:13])=[CH:4][C:3]=1B1OC(C)(C)C(C)(C)O1.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH:35]=[C:34](OS(C(F)(F)F)(=O)=O)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C([O-])([O-])=O.[Cs+].[Cs+]>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:24]([O:28][C:29]([N:31]1[CH2:32][CH:33]=[C:34]([C:3]2[CH:4]=[C:5]([O:11][CH:12]([CH3:13])[CH3:14])[C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=2[CH3:1])[CH2:35][CH2:36]1)=[O:30])([CH3:27])([CH3:25])[CH3:26]

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 597645312-(5-Isopropoxy-2-methyl-4-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Produkt 1

HCID 59764520tert-butyl 4-(5-isopropoxy-2-methyl-4-nitrophenyl)-5,6-dihydropyridine-1(2H)-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 18180031Water 1,2-dimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of 2-methyl-4-nitro-5-isopropoxy-phenylboronic acid pinacol ester (2.04 g, 6.4 mmol) and 4-Trifluoromethanesulfonyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (3.2 g, 9.6 mmol) in 110 mL of DME/H2O (10:1 V/V) is added Pd(PPh3)4 (365 mg, 0.32 mmol) and Cs2CO3 (4.2 g, 12.8 mmol). The reaction mixture is heated under N2 at 80° C. overnight. After cooling to room temperature, the reaction is filtered through Celite and the filtrate is diluted with 100 mL of EtOAc, sequentially washed with H2O, brine, and finally concentrated in vacuo. The crude product is purified by silica gel flash chromatography (5%-15% EtOAc in Hexanes as eluent) to afford 4-(5-Isopropoxy-2-methyl-4-nitro-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester as a yellow oil. 1H NMR (CD3OD, 400 Mz): 7.59 (s, 1H), 6.96 (s, 1H), 5.67 (broad s, 1H), 4.73 (m, 1H), 4.06 (m, 2H), 3.65 (m, 2H), 2.37 (m, 2H), 2.25 (s, 3H), 1.50 (s, 9H), 1.33 (d, J=6.0 Hz, 6H).

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. filtrationthe reaction is filtered through Celite
  3. additionthe filtrate is diluted with 100 mL of EtOAc
  4. washsequentially washed with H2O, brine
  5. concentrationfinally concentrated in vacuo
  6. customThe crude product is purified by silica gel flash chromatography (5%-15% EtOAc in Hexanes as eluent)

Quellen und Nachweise

ORD-Eintrag
ord-70065f31da5345b598cbf31461aa7891
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08957081B2

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