Dichloromethane → Cyclopentanecarboxylic acid, 2-[(4'-amino[1,1'-biphenyl]-4-yl)carbonyl]-, methyl ester, (1R,2R)-

HRID 9548

Reaktionsgleichung

Reaktionsgleichung von HRID 9548
Br[C:2]1[CH:18]=[CH:17][C:5]([C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[C:13]([O:15][CH3:16])=[O:14])=[O:7])=[CH:4][CH:3]=1.[NH2:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1.C([O-])([O-])=O.[Na+].[Na+].ClCCl>CCOC(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].CCO.C1(C)C=CC=CC=1>[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:2]2[CH:18]=[CH:17][C:5]([C:6]([C@@H:8]3[CH2:12][CH2:11][CH2:10][C@H:9]3[C:13]([O:15][CH3:16])=[O:14])=[O:7])=[CH:4][CH:3]=2)=[CH:22][CH:21]=1

Komponenten

9

Edukt 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27346154-Aminophenylboronic acidHCID 58681296(1R,2R)-Methyl 2-(4-bromobenzoyl)cyclopentanecarboxylate

Produkt 1

HCID 11416053Cyclopentanecarboxylic acid, 2-[(4'-amino[1,1'-biphenyl]-4-yl)carbonyl]-, methyl ester, (1R,2R)-Ausbeute 67,4 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 702EthanolLösungsmittelHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

Methyl trans-2-(4-bromobenzoyl)cyclopentanecarboxylate (1.60 g, 5.14 mmol) and 4-aminophenyl boronic acid (1.07 g, 6.17 mmol) were combined in a dry flask under argon. Toluene (25 mL), EtOH (10 mL), and 3 M aqueous Na2CO3 (8.50 mL, 25 mmol) were added and resulting solution was degassed for 30 minutes by using a flow of argon. Then [1,1′-bis(diphenylphosphino)-ferrocene]dichloro palladium(II), 1:1 complex with dichloromethane (419.9 mg, 0.51 mmol), was added and the resulting mixture was heated at 85° C. for 16 h. The mixture was cooled to it, diluted with EtOAc, and passed through a Celite® pad. The solvent was removed by rotary evaporation. Water and EtOAc were added and the aqueous layer was extracted with EtOAc. The combined organic phases were washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (Biotage Flash 40M) using 29 to 33% ethyl acetate in hexane to afford methyl trans-2-[(4′-amino-1,1′-biphenyl-4-yl)carbonyl]-cyclopentanecarboxylate (1.12 g, 67%). 1H NMR (400 MHz, CD2Cl2) δ 1.71–1.97 (m, 4H), 2.17 (m, 2H), 3.44 (m, 1H), 3.65 (s, 3H), 4.12 (m, 1H), 6.84 (m, 2H), 7.51 (m, 2H), 7.66 (m, 2H), 8.00 (m, 2H).

Aufarbeitung

  1. customresulting solution
  2. customwas degassed for 30 minutes
  3. temperatureThe mixture was cooled to it
  4. customThe solvent was removed by rotary evaporation
  5. additionWater and EtOAc were added
  6. extractionthe aqueous layer was extracted with EtOAc
  7. washThe combined organic phases were washed with water, brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash chromatography (Biotage Flash 40M)

Quellen und Nachweise

ORD-Eintrag
ord-9ea95650f399478f9361dfa1114d80a8
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07091228B2

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