Sodium hydride → tert-butyl (3R,6S)-6-(2,3-difluorophenyl)-1-[2-(methylthio)ethyl]-2-oxoazepan-3-ylcarbamate

HRID 20136

Reaktionsgleichung

Reaktionsgleichung von HRID 20136
[H-].[Na+].[F:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[C@H:11]1[CH2:17][NH:16][C:15](=[O:18])[C@H:14]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:13][CH2:12]1.I[CH2:28][CH2:29][S:30][CH3:31]>CN(C)C=O>[F:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[C@H:11]1[CH2:17][N:16]([CH2:28][CH2:29][S:30][CH3:31])[C:15](=[O:18])[C@H:14]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:25])[CH3:24])[CH2:13][CH2:12]1

Komponenten

5

Edukt 3

HCID 24758Sodium hydride4×HCID 156219881-Iodo-2-(methylsulfanyl)ethane3×HCID 23657400tert-Butyl [(3R,6S)-6-(2,3-difluorophenyl)-2-oxoazepan-3-yl]carbamate

Produkt 1

HCID 86595038tert-butyl (3R,6S)-6-(2,3-difluorophenyl)-1-[2-(methylthio)ethyl]-2-oxoazepan-3-ylcarbamateAusbeute 37,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
-30 °C

Versuchsvorschrift

Sodium hydride (60% dispersion in mineral oil; 40 mg, 0.600 mmol) was added to a solution of tert-butyl (3R,6S)-6-(2,3-difluorophenyl)-2-oxoazepan-3-ylcarbamate (170 mg, 0.500 mmol) in N,N-dimethylformamide (4 mL) at 0° C. After 5 min the mixture was cooled to −30° C. and 1-iodo-2-(methylthio)ethane [prepared according to known procedures: J. Org. Chem., 1987, 52, 2299-2301 (158 mg, 0.782 mmol)] was added. Additional sodium hydride (33 mg, 0.50 mmol) was added and after 4 h excess sodium hydride (33 mg, 0.50 mmol) and 1-iodo-2-(methylthio)ethane (75.6 mg, 0.374 mmol) were added. After 3 h, the final portions of sodium hydride (33 mg, 0.50 mmol) and 1-iodo-2-(methylthio)ethane (75.6 mg, 0.374 mmol) were added and the mixture stirred at −20° C. overnight. The reaction was quenched with water and the mixture was extracted with ethyl acetate. The organic layer was washed with water (3×), saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (0% ethyl acetate/hexanes→50% ethyl acetate/hexanes) gave the title compound (77 mg). MS 415 (M+1).

Aufarbeitung

  1. additionwere added
  2. customThe reaction was quenched with water
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with water (3×), saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (0% ethyl acetate/hexanes→50% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-c6a1db191d1940439816ea7d8c87c849
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745427B2

Verknüpfte Notizen

Wird geladen…