3,5-Bis(trifluoromethyl)benzylamine → 5-(3,5-Bis-trifluoromethyl-benzylamino)-8-chloro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester

HRID 2353967

Reaktionsgleichung

Reaktionsgleichung von HRID 2353967
[F:1][C:2]([F:16])([F:15])[C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)[CH2:6][NH2:7].[C:17]([O:21][C:22]([N:24]1[CH2:30][CH2:29][CH2:28][C:27](=O)[C:26]2[CH:32]=[CH:33][C:34]([Cl:36])=[CH:35][C:25]1=2)=[O:23])([CH3:20])([CH3:19])[CH3:18].[BH4-].[Na+]>CO.O.C(OCC)(=O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:17]([O:21][C:22]([N:24]1[CH2:30][CH2:29][CH2:28][CH:27]([NH:7][CH2:6][C:5]2[CH:4]=[C:3]([C:2]([F:15])([F:16])[F:1])[CH:10]=[C:9]([C:11]([F:14])([F:12])[F:13])[CH:8]=2)[C:26]2[CH:32]=[CH:33][C:34]([Cl:36])=[CH:35][C:25]1=2)=[O:23])([CH3:20])([CH3:18])[CH3:19]

Komponenten

8

Edukt 3

HCID 5210993,5-Bis(trifluoromethyl)benzylamineHCID 4311764Sodium borohydrideHCID 68678967tert-Butyl 8-chloro-5-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate

Produkt 1

HCID 866160825-(3,5-Bis-trifluoromethyl-benzylamino)-8-chloro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl esterAusbeute 93 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11026Titanium isopropoxideKatalysatorHCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Add 3,5-bis(trifluoromethyl)benzylamine (3.2 g, 13.1 mmol) followed by titanium isopropoxide (5.0 mL) to 8-Chloro-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester (3.5 g, 11.9 mmol) and stir at room temperature overnight. Dilute the mixture with 20 mL of Methanol and add sodium borohydride (23.8 mmol). Stir the suspension at room temperature for 1 h then dilute with water (200 mL) and ethyl acetate (200 mL). Filter the resulting emulsion through celite and wash with ethyl acetate (3×100 mL). Separate the organics and dry over sodium sulfate. Remove the solvent under vacuum and chromatograph the product over silica gel using ethyl acetate/hexane (5-30%) to elute. This affords the title compound (5.7 g, 93%) as an off white solid: MS (ES+): 523 (M+H).

Aufarbeitung

  1. stirringStir the suspension at room temperature for 1 h
  2. filtrationFilter the resulting emulsion through celite
  3. washwash with ethyl acetate (3×100 mL)
  4. customSeparate the organics and
  5. dry with materialdry over sodium sulfate
  6. customRemove the solvent under vacuum and chromatograph the product over silica gel
  7. washto elute

Quellen und Nachweise

ORD-Eintrag
ord-ad021bea2b2e41b897343e5b30b1b8ea
Quelldatensatz
uspto-grants-2010_07
Patentnummer
US07749992B2

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