Potassium Carbonate → 4-[7-Chloro-1-oxo-2-(4-trifluoromethoxybenzyl)-2,3-dihydro-1H-isoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 2427517Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2427517
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([Cl:11])[CH:10]=1)[C:7](=[O:12])[N:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=1)[CH2:5]2.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:25]([O:29][C:30]([N:32]1[CH2:33][CH:34]=[C:35]([C:2]2[CH:3]=[C:4]3[C:8](=[C:9]([Cl:11])[CH:10]=2)[C:7](=[O:12])[N:6]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]([F:23])([F:22])[F:24])=[CH:16][CH:15]=2)[CH2:5]3)[CH2:36][CH2:37]1)=[O:31])([CH3:28])([CH3:26])[CH3:27]

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 117044755-Bromo-7-chloro-2-(4-trifluoromethoxybenzyl)-2,3-dihydroisoindol-1-one

Produkt 1

HCID 579494284-[7-Chloro-1-oxo-2-(4-trifluoromethoxybenzyl)-2,3-dihydro-1H-isoindol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl esterAusbeute 23,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

5-Bromo-7-chloro-2-(4-trifluoromethoxybenzyl)-2,3-dihydroisoindol-1-one (190.0 mg, 0.452 mmol), 4-(4,4,5,5-Tetramethyl-[1,3,2]-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert butyl ester (140.0 mg, 0.452 mmol), potassium carbonate (187.0 mg, 1.36 mmol), and PdCl2(dppf) (37.0 mg, 0.045 mmol) were suspended in anhydrous dimethyl formamide (2 mL) and the mixture was heated to 110° C. After nineteen hours, the heating was stopped and the cooled reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with water and brine, dried over magnesium sulfate, filtered and concentrated. The product was purified by column chromatography (30% EtOAc/Hexanes) to provide the title compound as a colourless solid (55.0 mg, 23%.) 1H NMR (300 MHz, CDCl3): δ 7.38 (m, 3H), 7.26 (s, 1H), 7.18 (d, 2H), 6.18 (broad s, 1H), 4.79 (s, 2H), 4.25 (s, 2H), 4.11 (broad s, 2H), 3.65 (t, 2H), 2.5 (broad s, 2H), 1.49 (s, 9H).

Aufarbeitung

  1. waitAfter nineteen hours
  2. customthe cooled reaction mixture
  3. customwas partitioned between ethyl acetate and water
  4. washThe organic phase was washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe product was purified by column chromatography (30% EtOAc/Hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-5419c4aefe4a455f877e84e3cacd5ae1
Quelldatensatz
uspto-grants-2011_06
Patentnummer
US07968570B2

Notizen zur Reaktion

Wird geladen…