1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → tert-butyl (1R,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane-6-carboxylate

HRID 495087Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 495087
[C@@H:1]12[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@@H:5]1[CH2:4][NH:3][CH2:2]2.Br[C:16]1[CH:17]=[C:18]([Cl:23])[C:19]([Cl:22])=[N:20][CH:21]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:23][C:18]1[CH:17]=[C:16]([N:3]2[CH2:4][C@@H:5]3[C@@H:1]([CH2:7][N:6]3[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:2]2)[CH:21]=[N:20][C:19]=1[Cl:22]

Komponenten

7

Edukt 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 127477605-Bromo-2,3-dichloropyridineHCID 23635158HCID 23635158, VerbindungHCID 23676156Sodium t-butoxide

Produkt 1

HCID 23634672tert-butyl (1R,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane-6-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
87.5 °C

Versuchsvorschrift

A 1 L flask with mechanical stirrer was charged with a solution of tert-butyl (1R,5S)-3,6-diazabicyclo[3.2.0]heptane-6-carboxylate (10.0 g, 50 mmol, product of Example 1L) and 5-bromo-2,3-dichloropyridine (14.0 g, from Example 2D) in toluene (400 mL). The flask was evacuated and purged three times with nitrogen. Xantphos (1.74 g, 3 mmol), Pd2(dba)3 (916 mg, 1 mmol) and sodium tert-butoxide (7.20 g, 75 mmol) were added successively to the flask against a purge of nitrogen gas. The flask was again evacuated and purged with nitrogen (3 times) and the mixture heated to 85-90° C. under N2. After 2 hours, the reaction was cooled to room temperature, diluted with ethyl acetate (1000 mL) and water (200 mL), and stirred for 5 minutes. The organic phase was separated, washed with brine (200 mL), dried (MgSO4), filtered through Celite® (diatomaceous earth) and the filtrate concentrated under vacuum to provide the title compound which was used in the next step without further purification. 1H NMR (MeOH-d4, 300 MHz) δ 1.45 (s, 9H), 2.94 (dd, J=1.6, 4.4 Hz, 1H), 3.04 (dd, J=10.2, 6.4 Hz, 1H), 3.3 (m, 1H), 3.58 (m, 1H), 3.78 (d, J=10.5 Hz, 1H), 3.90 (d, J=10.8 Hz, 1H), 4.05 (m, 1H), 4.83 (m, 1H) 7.39 (d, J=2.7 Hz, 1H), 7.84 (d, J=2.7 Hz, 1H); MS (DCI/NH3) m/z 344/346/348 (M+H)+.

Aufarbeitung

  1. customThe flask was evacuated
  2. custompurged three times with nitrogen
  3. customa purge of nitrogen gas
  4. customThe flask was again evacuated
  5. custompurged with nitrogen (3 times)
  6. temperaturethe reaction was cooled to room temperature
  7. additiondiluted with ethyl acetate (1000 mL) and water (200 mL)
  8. customThe organic phase was separated
  9. washwashed with brine (200 mL)
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered through Celite® (diatomaceous earth)
  12. concentrationthe filtrate concentrated under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-0e617cc0f32c4a9e96f72b041bb177ba
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07538226B2

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