3,5-Bis(trifluoromethyl)benzylamine → 5-(3,5-Bis-trifluoromethyl-benzylamino)-7-bromo-8-chloro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester

HRID 2353912Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2353912
[CH:1]([O:4][C:5]([N:7]1[CH2:13][CH2:12][CH2:11][C:10](=O)[C:9]2[CH:15]=[C:16]([Br:20])[C:17]([Cl:19])=[CH:18][C:8]1=2)=[O:6])([CH3:3])[CH3:2].[F:21][C:22]([F:36])([F:35])[C:23]1[CH:24]=[C:25]([CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:30]=1)[CH2:26][NH2:27].C([BH3-])#N.[Na+]>CO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH:1]([O:4][C:5]([N:7]1[CH2:13][CH2:12][CH2:11][CH:10]([NH:27][CH2:26][C:25]2[CH:28]=[C:29]([C:31]([F:32])([F:33])[F:34])[CH:30]=[C:23]([C:22]([F:21])([F:35])[F:36])[CH:24]=2)[C:9]2[CH:15]=[C:16]([Br:20])[C:17]([Cl:19])=[CH:18][C:8]1=2)=[O:6])([CH3:3])[CH3:2]

Komponenten

6

Edukt 3

HCID 5210993,5-Bis(trifluoromethyl)benzylamineHCID 5003444Sodium cyanoborohydrideHCID 686772987-Bromo-8-chloro-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester

Produkt 1

HCID 866160695-(3,5-Bis-trifluoromethyl-benzylamino)-7-bromo-8-chloro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl esterAusbeute 91,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11026Titanium isopropoxideKatalysatorHCID 887MethanolLösungsmittel

Versuchsvorschrift

A mixture of 7-Bromo-8-chloro-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (0.98 g, 2.72 mmole), 3,5-bistrifluoromethyl benzyl amine (0.682 g, 2.72 mmol) and titanium(IV) isopropoxide (1.00 ml, 3.26 mmol) was stirred at room temperature overnight. To it was added sodium cyanoborohydride (0.684 g, 10.9 mmole) in MeOH (20.0 ml) and the reaction was continued at room temperature for 6 hours. The mixture was partitioned between ethyl acetate (50.0 ml) and water (50.0 ml). The precipitate was removed by filtration. The aqueous layer was extracted with more ethyl acetate (2×50.0 ml). The combined organics washed with brine (3×150 ml). Dried over Na2SO4, filtered and concentrated to provide the crude product (1.47 g, 88%), which was used directly for the next step without further purification. MS (ES+): 587, 589 (M+H).

Aufarbeitung

  1. waitthe reaction was continued at room temperature for 6 hours
  2. customThe mixture was partitioned between ethyl acetate (50.0 ml) and water (50.0 ml)
  3. customThe precipitate was removed by filtration
  4. extractionThe aqueous layer was extracted with more ethyl acetate (2×50.0 ml)
  5. washThe combined organics washed with brine (3×150 ml)
  6. dry with materialDried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-49ed07fe3e8d46739b41a052360063da
Quelldatensatz
uspto-grants-2010_07
Patentnummer
US07749992B2

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