Ethyl Acetate → (5R)-3-[4-(1,1-Dioxo-2,5-dihydrothien-3-yl)-3-fluorophenyl]-5-[4-methyl-1,2,3-triazol-1-ylmethyl]oxazolidin-2-one

HRID 1452568Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1452568
[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:13][C@H:12]([CH2:14][N:15]3[CH:19]=[C:18]([CH3:20])[N:17]=[N:16]3)[O:11][C:10]2=[O:21])[CH:5]=[CH:6][C:7]=1I.[O:22]=[S:23]1(=[O:45])[CH2:28][CH:27]=[C:26](C2C(F)=CC(N3C[C@H](CN)OC3=O)=CC=2F)C[CH2:24]1.[F-].[K+].C(OCC)(=O)C>CN1CCCC1=O.[Cu]I.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>[O:45]=[S:23]1(=[O:22])[CH2:24][CH:26]=[C:27]([C:7]2[CH:6]=[CH:5][C:4]([N:9]3[CH2:13][C@H:12]([CH2:14][N:15]4[CH:19]=[C:18]([CH3:20])[N:17]=[N:16]4)[O:11][C:10]3=[O:21])=[CH:3][C:2]=2[F:1])[CH2:28]1

Komponenten

8

Edukt 4

HCID 8857Ethyl AcetateHCID 522689Potassium FluorideHCID 57526977(5S)-3-[4-(1,1-Dioxo-3,6-dihydro-2H-thiopyran-4-yl)-3,5-difluorophenyl]-5-(aminomethyl)-oxazolidin-2-oneHCID 58778315(5R)-3-(3-Fluoro-4-iodophenyl)-5-[4-methyl-1,2,3-triazol-1-ylmethyl]oxazolidin-2-one2×

Produkt 1

HCID 57527012(5R)-3-[4-(1,1-Dioxo-2,5-dihydrothien-3-yl)-3-fluorophenyl]-5-[4-methyl-1,2,3-triazol-1-ylmethyl]oxazolidin-2-oneAusbeute 10,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 13387N-methyl-2-pyrrolidoneLösungsmittel2×

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

(5R)-3-(3-Fluoro-4-iodophenyl)-5-[4-methyl-1,2,3-triazol-1-ylmethyl]oxazolidin-2-one (Intermediate 13) (200 mg, 0.50 mmol) and copper (I) iodide (39 mg, 0.20 mmol) were dissolved in dry 1-methyl-2-pyrrolidinone (2 ml) and the reaction mixture placed under an atmosphere of argon. TetrakiS(triphenylphosphine)palladium(0) (35 mg, 0.05 mmol) was added, followed by a solution of tributyl(1,1-dioxo-2,5-dihydrothien-3-yl)stannane [Bew, Sean P.; Sweeney, J. B., Synthesis (1994), (7), p698] (263 mg, 0.65 mmol) in 1-methyl-2-pyrrolidinone (2 ml) and the reaction mixture stirred for 5 days at 40° C. Aqueous potassium fluoride 1M (150 ml) and ethyl acetate (150 ml) were added and the insoluble materials filtered off. The ethyl acetate layer was separated, dried over magnesium sulphate, filtered then concentrated in vacuo onto Isolute HM-N (2 g). Purification by chromatography on silica gel with 1.5% methanol in dichloromethane gave 20 mg (10%) of the desired compound.

Aufarbeitung

  1. filtrationthe insoluble materials filtered off
  2. customThe ethyl acetate layer was separated
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationthen concentrated in vacuo onto Isolute HM-N (2 g)
  6. customPurification by chromatography on silica gel with 1.5% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-e2343ad8696141e298fcfb6a70a90c43
Quelldatensatz
uspto-grants-2009_01
Patentnummer
US07473699B2

Notizen zur Reaktion

Wird geladen…