Triphenylphosphine → (1S,4R)-4-(4,7-difluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enol

HRID 470171

Reaktionsgleichung

Reaktionsgleichung von HRID 470171
[F:1][C:2]1[C:7]2[N:8]=[CH:9][NH:10][C:6]=2[C:5]([F:11])=[CH:4][N:3]=1.[H-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC([O:36][C@H:37]1[CH:41]=[CH:40][C@@H:39](O)[CH2:38]1)=O>CN(C=O)C.C1COCC1.CCOC(C)=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>[F:1][C:2]1[C:7]2[N:8]=[CH:9][N:10]([C@@H:40]3[CH2:41][C@H:37]([OH:36])[CH:38]=[CH:39]3)[C:6]=2[C:5]([F:11])=[CH:4][N:3]=1

Komponenten

9

Edukt 4

HCID 11776TriphenylphosphineHCID 24758Sodium hydrideHCID 10154103rac-(1R,4S)-4-hydroxycyclopent-2-en-1-yl acetateHCID 178506010HCID 178506010, Verbindung

Produkt 1

HCID 58329283(1S,4R)-4-(4,7-difluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enol

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

4,7-difluoro-1H-imidazo[4,5-c]pyridine (1-4) (2.0 g, 12.9 mmol, 1 equiv) was dissolved in dry DMF (21 mL). Sodium hydride (542 mg, 13.5 mmol, 1.05 equiv) was carefully added. The resulting mixture was stirred at ambient temperature for 45 minutes at which point triphenylphosphine (507 mg, 1.9 mmol, 0.15 equiv), Pd-tetrakis (745 mg, 0.6 mmol, 0.05 equiv) and (1R,3S)-(+)-cis-4-cyclopentene-1,3-diol 1-acetate (3-1) (2.2 g, 15.5 mmol, 1.2 equiv) in dry THF (21 mL) were added. The mixture was stirred at 60° C. for 16 hours, then cooled to ambient temperature, diluted with 100 mL EtOAc and washed with 50 mL water. The aqueous layer was washed with EtOAc three additional times, and the combined washings were dried over MgSO4, filtered and concentrated. The crude residue was purified by reverse phase chromatography (5-95% CH3CN/water with 0.1% TFA modifier) to afford (1S,4R)-4-(4,7-difluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enol (3-2) as a white solid. LRMS m/z (M+H) 238.0 found, 238.1 required.

Aufarbeitung

  1. additionwere added
  2. temperaturecooled to ambient temperature
  3. washwashed with 50 mL water
  4. washThe aqueous layer was washed with EtOAc three additional times
  5. dry with materialthe combined washings were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by reverse phase chromatography (5-95% CH3CN/water with 0.1% TFA modifier)

Quellen und Nachweise

ORD-Eintrag
ord-99a7170ad43d48d4bcf9588f4f702bd6
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08629275B2

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