Cesium fluoride → (S)-(3-chloro-5-trifluoromethyl-benzyl)-(7,9-dimethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine

HRID 507181Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 507181
Br[C:2]1[C:7]2[NH:8][CH2:9][CH2:10][CH2:11][C@H:12]([N:13]([CH2:20][C:21]3[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([Cl:31])[CH:22]=3)[C:14]3[N:15]=[N:16][N:17]([CH3:19])[N:18]=3)[C:6]=2[CH:5]=[C:4]([CH3:32])[C:3]=1[C:33]([F:36])(F)[F:34].[CH3:37]B(O)O.[F-:41].[Cs+]>O1CCOCC1.C(OCC)(=O)C.[Cl-].[Cl-].C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2].[Pd+2]>[Cl:31][C:23]1[CH:22]=[C:21]([CH:26]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:24]=1)[CH2:20][N:13]([C@H:12]1[CH2:11][CH2:10][CH2:9][NH:8][C:7]2[C:2]([CH3:37])=[C:3]([C:33]([F:34])([F:36])[F:41])[C:4]([CH3:32])=[CH:5][C:6]1=2)[C:14]1[N:15]=[N:16][N:17]([CH3:19])[N:18]=1

Komponenten

7

Edukt 3

HCID 25953Cesium fluorideHCID 139377Methylboronic AcidHCID 59432411(S)-(9-bromo-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(3-chloro-5-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amine

Produkt 1

HCID 59432530(S)-(3-chloro-5-trifluoromethyl-benzyl)-(7,9-dimethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amineAusbeute 92,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178478644HCID 178478644, VerbindungKatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

Add a solution of (S)-(9-bromo-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(3-chloro-5-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amine (0.39 g, 0.65 mmol) in dioxane (5 mL) to a mixture of methylboronic acid (0.12 g, 1.96 mmol), palladium diphenylphosphinoferrocene dichloride (0.05 g, 0.06 mmol), and cesium fluoride (0.35 g, 2.32 mmol), then purge with nitrogen and stir for 15 min. at room temperature, then at 100° C. for 4 h. After completion, cool the reaction to room temperature, dilute with ethyl acetate (50 mL) and wash with water and brine (10 mL each). Dry the organic layer over sodium sulfate, filter, and remove the solvent under reduced pressure. Purify the residue using flash column chromatography on silica gel, eluting with hexanes/ethyl acetate (0-30% EtOAc in hexane), to provide the title compound as a white solid (0.32 g, 90%). MS (ES+): 533 (M+H).

Aufarbeitung

  1. custompurge with nitrogen
  2. waitat 100° C. for 4 h
  3. temperatureAfter completion, cool
  4. customthe reaction to room temperature
  5. washwash with water and brine (10 mL each)
  6. dry with materialDry the organic layer over sodium sulfate
  7. filtrationfilter
  8. customremove the solvent under reduced pressure
  9. customPurify the residue
  10. washeluting with hexanes/ethyl acetate (0-30% EtOAc in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-0e19c3b446a44ceba82668720c7e4855
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07786108B2

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