Cesium carbonate → tert-butyl N-(4-fluoropyridin-2-yl)carbamate

HRID 706616

Reaktionsgleichung

Reaktionsgleichung von HRID 706616
Cl[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][N:3]=1.[C:9](=[O:16])([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[NH2:10].C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.O1CCCC1>[F:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:10][C:9](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:7]=1

Komponenten

7

Edukt 3

HCID 10796Cesium carbonate2×HCID 77922tert-Butyl carbamateHCID 27827922-Chloro-4-fluoropyridine

Produkt 1

HCID 51354888tert-butyl N-(4-fluoropyridin-2-yl)carbamateAusbeute 70,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A flask was charged with 2-chloro-4-fluoropyridine (20 g, 152 mmol), tert-butyl carbamate (89 g, 760 mmol), tris(dibenzylideneacetone)dipalladium (1.39 g, 1.52 mmol), X-PHOS (1.48 g, 3.10 mmol), cesium carbonate (99 g, 588 mmol), and tetrahydrofuran (500 mL) under an atmosphere of dry nitrogen. This mixture was refluxed under nitrogen for 7 hours. An additional equivalent of cesium carbonate was added to drive reaction to completion. The mixture was cooled to ambient temperature and filtered through Celite, and the Celite was washed with ethyl acetate. The filtrate was partitioned between saturated sodium bicarbonate and ethyl acetate. The aqueous layer was washed with ethyl acetate twice. The combined organics were washed with brine and dried with sodium sulfate, concentrated under vacuum, and purified by column chromatography to give tert-butyl 4-fluoropyridin-2-ylcarbamate as a pale yellow solid (22.6 g).

Aufarbeitung

  1. temperatureThis mixture was refluxed under nitrogen for 7 hours
  2. customreaction to completion
  3. filtrationfiltered through Celite
  4. washthe Celite was washed with ethyl acetate
  5. customThe filtrate was partitioned between saturated sodium bicarbonate and ethyl acetate
  6. washThe aqueous layer was washed with ethyl acetate twice
  7. washThe combined organics were washed with brine
  8. dry with materialdried with sodium sulfate
  9. concentrationconcentrated under vacuum
  10. custompurified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-e654febe1aab4a7ba5538020f8811df5
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09174981B2

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