Cesium carbonate → 2,2-dichloro-1-((4S,5R)-4-(fluoromethyl)-5-(4-(6-(hydroxymethyl)pyridin-3-yl)phenyl)-2,2-dimethyloxazolidin-3-yl)ethanone

HRID 1500273Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1500273
[OH:1][CH2:2][C:3]1[N:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.[Cl:12][CH:13]([Cl:32])[C:14]([N:16]1[C@H:20]([CH2:21][F:22])[C@@H:19]([C:23]2[CH:28]=[CH:27][C:26](I)=[CH:25][CH:24]=2)[O:18][C:17]1([CH3:31])[CH3:30])=[O:15].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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>[Cl:32][CH:13]([Cl:12])[C:14]([N:16]1[C@H:20]([CH2:21][F:22])[C@@H:19]([C:23]2[CH:28]=[CH:27][C:26]([C:6]3[CH:7]=[N:8][C:3]([CH2:2][OH:1])=[CH:4][CH:5]=3)=[CH:25][CH:24]=2)[O:18][C:17]1([CH3:30])[CH3:31])=[O:15]

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 441182556-(Hydroxymethyl)pyridine-3-boronic acidHCID 86695394(4S,5R)-3-(dichloroacetyl)-4-(fluoromethyl)-5-(4-iodophenyl)-2,2-dimethyl-1,3-oxazolidine

Produkt 1

HCID 866954062,2-dichloro-1-((4S,5R)-4-(fluoromethyl)-5-(4-(6-(hydroxymethyl)pyridin-3-yl)phenyl)-2,2-dimethyloxazolidin-3-yl)ethanoneAusbeute 41,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel2×HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of commercially available (6-(hydroxymethyl)pyridin-3-yl)boronic acid (1.020 g, 5.38 mmol), 2,2-dichloro-1-((4S,5R)-4-(fluoromethyl)-5-(4-iodophenyl)-2,2-dimethyloxazolidin-3-yl)ethanone (2.0 g mg, 4.48 mmol), Cs2CO3 (4.38 g, 13.4 mmol) in dioxane (40 mL) and water (25 mL) is bubbled with nitrogen gas for 2 minutes. To this mixture is added Pd(PPh3)4 (518 mg, 0.44 mmol) and the resulting reaction mixture heated to 80° C. in microwave reactor for 6 hours. The reaction is diluted with water (20 ml) and extracted with ethyl acetate (3×20 mL). The combined organic solution is dried over Na2SO4 and concentrated. The crude product is adsorbed on celite, and purified on silica gel column using 0 to 50% EtOAC/heptane to give the title compound (800 mg): LCMS m/z (Cl): 427 [M+H].

Aufarbeitung

  1. customis bubbled with nitrogen gas for 2 minutes
  2. customthe resulting reaction mixture
  3. extractionextracted with ethyl acetate (3×20 mL)
  4. dry with materialThe combined organic solution is dried over Na2SO4
  5. concentrationconcentrated
  6. custompurified on silica gel column

Quellen und Nachweise

ORD-Eintrag
ord-777741dc874b49f7a5f2150da421ff96
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09206126B2

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