Sodium Carbonate → 2-(4-((2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)methyl)phenyl)acetic acid

HRID 1508777Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1508777
Cl.Cl[C:3]1[CH:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[CH:10]=2)[N:6]=[C:5]2[CH2:16][CH2:17][CH2:18][C:4]=12.CC1(C)C(C)(C)OB([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([CH2:34][C:35]([O:37]C)=[O:36])=[CH:30][CH:29]=2)O1.C([O-])([O-])=O.[Na+].[Na+].O1CCOCC1>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].O>[Cl:15][C:11]1[CH:10]=[C:9]([C:7]2[N:6]=[C:5]3[CH2:16][CH2:17][CH2:18][C:4]3=[C:3]([CH2:27][C:28]3[CH:29]=[CH:30][C:31]([CH2:34][C:35]([OH:37])=[O:36])=[CH:32][CH:33]=3)[CH:8]=2)[CH:14]=[CH:13][CH:12]=1

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 674944814-(2-Methoxy-2-oxoethyl)benzylboronic Acid Pinacol EsterHCID 901118224-chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine HCl salt

Produkt 1

HCID 903385752-(4-((2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)methyl)phenyl)acetic acidAusbeute 53,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A 10-mL sealed tube, with stirrer bar, was charged with 4-chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine hydrochloride (0.100 g, 0.33 mol), methyl 2-(4-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)phenyl)acetate (0.096 g, 0.33 mmol), Pd(dppf)Cl2 (0.027 g, 0.033 mmol), and powdered Na2CO3 (0.141 g, 1.33 mmol). Dioxane (3 mL) and water (1.5 mL) were added. The resulting mixture was stirred under Ar at 90° C. for 3 d. until the starting chloride was consumed. After cooling to room temperature, the reaction mixture was adsorbed onto silica (4 g). Purification by chromatography on silica using dichloromethane/methanol (10:0 to 8:2) as eluent afforded the title compound (0.067 g, 53%) as a light brown solid. MW=377.86. 1H NMR (DMSO-d6, 500 MHz) δ 12.24 (br s, 1H), 8.09-8.07 (m, 1H), 8.00-7.97 (m, 1H), 7.70 (s, 1H), 7.51-7.42 (m, 2H), 7.25-7.16 (m, 2H), 7.15-7.09 (m, 2H), 3.97 (s, 2H), 3.51 (s, 2H), 2.94 (t, J=7.5 Hz, 2H), 2.84 (t, J=7.5 Hz, 2H), 2.09-2.01 (m, 2H); ESI MS m/z 378 [M+H]+.

Aufarbeitung

  1. customA 10-mL sealed tube
  2. customuntil the starting chloride was consumed
  3. temperatureAfter cooling to room temperature
  4. customPurification by chromatography on silica

Quellen und Nachweise

ORD-Eintrag
ord-0d5c2c9d6da3427b9ad3ad64ff9b3355
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09221843B2

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