Dichloromethane → 5-{5-[(4-benzyl-4-hydroxypiperidin-1-yl)methyl]2-thienyl}2-tertbutylisothiazol-3(2H)-one 1,1-dioxide trifluoroacetate

HRID 724621Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 724621
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([C:15]1([OH:30])[CH2:20][CH2:19][N:18]([CH2:21][C:22]2[S:26][C:25](B(O)O)=[CH:24][CH:23]=2)[CH2:17][CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:31]([N:35]1[C:39](=[O:40])[CH:38]=[C:37](Cl)[S:36]1(=[O:43])=[O:42])([CH3:34])([CH3:33])[CH3:32].C(=O)([O-])[O-].[K+].[K+].ClCCl>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]>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([C:15]1([OH:30])[CH2:20][CH2:19][N:18]([CH2:21][C:22]2[S:26][C:25]([C:37]3[S:36](=[O:42])(=[O:43])[N:35]([C:31]([CH3:33])([CH3:32])[CH3:34])[C:39](=[O:40])[CH:38]=3)=[CH:24][CH:23]=2)[CH2:17][CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Komponenten

7

Edukt 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 218786382-Tert-butyl-5-chloro-2,3-dihydro-1lambda6,2-thiazole-1,1,3-trioneHCID 69597789{5-[(4-Benzyl-4-hydroxypiperidin-1-yl)methyl]-2-thienyl}boronic acid trifluoroacetate

Produkt 1

HCID 695978815-{5-[(4-benzyl-4-hydroxypiperidin-1-yl)methyl]2-thienyl}2-tertbutylisothiazol-3(2H)-one 1,1-dioxide trifluoroacetateAusbeute 17 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A solution of 4.12-A (100 mg, 0.2 mmol), 9-A (55 mg, 0.25 mmol), potassium carbonate (190 mg, 1.3 mmol) in 1,4-dioxane (1.5 mL) was added to a vial and degassed with nitrogen. Then [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (28 mg, 0.034 mmol) was added, degassed with nitrogen and the vial capped and heated at 80° C. overnight. The reaction mixture was filtered through silica gel and eluted with copious amounts of EtOAc. The solvent was concentrated and crude sample purified by reverse phase HPLC to afford 20 mg (15%) of 4.12-B. LCMS found for C24H30N2O4S2 (M+H)+: m/z=475.

Aufarbeitung

  1. customdegassed with nitrogen
  2. customdegassed with nitrogen
  3. customthe vial capped
  4. filtrationThe reaction mixture was filtered through silica gel
  5. washeluted with copious amounts of EtOAc
  6. concentrationThe solvent was concentrated
  7. customcrude sample purified by reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-5da0916eddb9466d8523fdbf9746e7dc
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07141596B2

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