Cesium carbonate → Methyl 2-{[3'-fluoro-4'-(formylamino)-1,1'-biphenyl-4-yl]carbonyl}cyclopentanecarboxylate

HRID 30867

Reaktionsgleichung

Reaktionsgleichung von HRID 30867
[F:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][C:3]=1[NH:9][CH:10]=[O:11].C([O-])(=O)C.[K+].Br[C:18]1[CH:34]=[CH:33][C:21]([C:22]([C@@H:24]2[CH2:28][CH2:27][CH2:26][C@H:25]2[C:29]([O:31][CH3:32])=[O:30])=[O:23])=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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>[F:1][C:2]1[CH:7]=[C:6]([C:18]2[CH:19]=[CH:20][C:21]([C:22]([CH:24]3[CH2:28][CH2:27][CH2:26][CH:25]3[C:29]([O:31][CH3:32])=[O:30])=[O:23])=[CH:33][CH:34]=2)[CH:5]=[CH:4][C:3]=1[NH:9][CH:10]=[O:11]

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 23549341N-(2-fluoro-4-iodophenyl)formamideHCID 58681296(1R,2R)-Methyl 2-(4-bromobenzoyl)cyclopentanecarboxylate

Produkt 1

HCID 21985795Methyl 2-{[3'-fluoro-4'-(formylamino)-1,1'-biphenyl-4-yl]carbonyl}cyclopentanecarboxylateAusbeute 169,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a suspension of 2-fluoro-4-iodophenylformamide (5.11 g, 19.28 mmol) bis(pinacolato)diboron (4.89 g, 19.28 mmol), potassium acetate (5.67 g, 57.84 mmol), and palladium acetate (129 mg, 0.58 mmol) in N,N-dimethylformamide (125 mL) was bubbled through argon for 30 minutes. The reaction mixture was then heated at 80° C. for 3 h. After the mixture was cooled to rt, methyl (R,R)-2-(4-bromobenzoyl)cyclopentanecarboxylate (2.2 g, 7.35 mmol, 97% ee), tetrakis(triphenylphosphine)palladium(0) (668 mg, 0.58 mmol), and cesium carbonate (9.43 g, 28.92 mmol) were added, and the reaction mixture was then heated at 80° C. for 16 h. The mixture was then cooled to rt, quenched with water, extracted with ethyl acetate, and dried over anhydrous sodium sulfate. Solvent was then removed under reduced pressure and the crude product was purified by flash chromatography (Biotage 75) using 1:1 ethylacetate/hexane to afford methyl 2-{[3′-fluoro-4′-(formylamino)-1,1′-biphenyl-4-yl]carbonyl}cyclopentanecarboxylate (4.6 g, 65%). LC-MS ret. time 3.15 min, m/z 342.0 (MH+); 1H NMR (300 MHz, DMSO-d6) δ 1.52-1.94 (m, 1H), 1.92-2.07 (m, 1H), 2.10-2.21 (m, 1H), 3.48 (m, 1H), 3.55 (s, 3H), 4.12 (q, 1H), 7.59 (dd, 1H), 7.62 (dd, 1H), 7.87 (d, 2H), 8.09 (d, 2H), 8.25 (t, 1H), 8.34 (s, 1H), 10.62 (s, 1H).

Aufarbeitung

  1. customwas bubbled through argon for 30 minutes
  2. temperatureAfter the mixture was cooled to rt
  3. temperaturethe reaction mixture was then heated at 80° C. for 16 h
  4. temperatureThe mixture was then cooled to rt
  5. customquenched with water
  6. extractionextracted with ethyl acetate
  7. dry with materialdried over anhydrous sodium sulfate
  8. customSolvent was then removed under reduced pressure
  9. customthe crude product was purified by flash chromatography (Biotage 75)

Quellen und Nachweise

ORD-Eintrag
ord-97bc0bc93b3a43249beb6d8099feba1f
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07423156B2

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