Sodium hydride → 1,1-Dimethylethyl N-((3R,6S)-6-(2,3-difluorophenyl)hexahydro-2-oxo-1-(2,2,2-trifluoroethyl)-1H-azepin-3-yl)carbamate

HRID 133130

Reaktionsgleichung

Reaktionsgleichung von HRID 133130
[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.ClC(Cl)(Cl)S(O[CH2:33][C:34]([F:37])([F:36])[F:35])(=O)=O>CN(C=O)C>[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]([CH2:33][C:34]([F:37])([F:36])[F:35])[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 hydride2×HCID 900272,2,2-Trifluoroethyl trichloromethanesulphonate2×HCID 23657400tert-Butyl [(3R,6S)-6-(2,3-difluorophenyl)-2-oxoazepan-3-yl]carbamate

Produkt 1

HCID 865950421,1-Dimethylethyl N-((3R,6S)-6-(2,3-difluorophenyl)hexahydro-2-oxo-1-(2,2,2-trifluoroethyl)-1H-azepin-3-yl)carbamate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Sodium hydride (60% dispersion in mineral oil, 70.7 mg, 1.06 mmol) was added to a solution of tert-butyl (3R,6S)-6-(2,3-difluorophenyl)-2-oxoazepan-3-ylcarbamate from Step E (301 mg, 0.884 mmol) in DMF (7 mL) at −35° C. After 15 min, 2,2,2-trifluoroethyl trichloromethanesulfonate (0.314 mL, 1.91 mmol) was added and stirring was continued at −35° C. After 30 min, additional sodium hydride (27 mg, 0.40 mmol) and 2,2,2-trifluoroethyl trichloromethanesulfonate (0.140 mL, 0.85 mmol) were added. After 2 h, the reaction was quenched with H2O and the mixture was extracted with EtOAc. The organic layer was washed with water (3×), then brine, then dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—100:0 to 70:30, to give the title compound. MS: m/z=423 (M+1).

Aufarbeitung

  1. customwas continued at −35° C
  2. waitAfter 30 min
  3. waitAfter 2 h
  4. customthe reaction was quenched with H2O
  5. extractionthe mixture was extracted with EtOAc
  6. washThe organic layer was washed with water (3×)
  7. dry with materialbrine, then dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by silica gel chromatography
  11. washeluting with a gradient of hexane

Quellen und Nachweise

ORD-Eintrag
ord-a885a7f6fcbd4be390bc07607be3d3f1
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07390798B2

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