Hydrochloric Acid → HCID 59003238, compound

HRID 2353949Notes

Reaction equation

HRID 2353949 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:13][CH2:12][CH2:11][C:10](=O)[C:9]2[CH:15]=[CH:16][C:17]([Br:20])=[C:18]([CH3:19])[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].[BH4-].[Na+].[OH-].[Na+].[C:41](OC(=O)C)(=[O:43])[CH3:42].N1C=CC=CC=1.Cl>ClCCl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].CO>[CH:1]([O:4][C:5]([N:7]1[CH2:13][CH2:12][CH2:11][CH:10]([N:27]([C:41](=[O:43])[CH3:42])[CH2:26][C:25]2[CH:24]=[C:23]([C:22]([F:35])([F:36])[F:21])[CH:30]=[C:29]([C:31]([F:34])([F:32])[F:33])[CH:28]=2)[C:9]2[CH:15]=[CH:16][C:17]([Br:20])=[C:18]([CH3:19])[C:8]1=2)=[O:6])([CH3:3])[CH3:2]

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 7918Acetic AnhydrideHCID 14798Sodium HydroxideHCID 5210993,5-Bis(trifluoromethyl)benzylamineHCID 4311764Sodium borohydrideHCID 59432457HCID 59432457, compound

Product 1

HCID 59003238HCID 59003238, compoundYield 10.3%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Inject titanium isopropoxide (1.1 mL, 3.89 mmol) to a mixture of 8-bromo-9-methyl-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (882 mg, 2.59 mmol) and 3,5-bis(trifluoromethyl)benzylamine (866 mg, 2.85 mmol) at room temperature under an atmosphere of nitrogen and stir the solution for 14 h. Add methanol (11.3 mL) and sodium borohydride (245 mg, 6.47 mmol) and stir the mixture under nitrogen at room temperature for 2 h. Add 0.1M NaOH (61 mL), stir for 30 min. Filter through celite and wash the residue with AcOEt. Separate organic layer, extract aqueous with AcOEt. Wash organic layer with brine and dry the organic layers over anhydrous magnesium sulfate. Filter and remove the solvent under reduced pressure. To the former crude in dichloromethane (9.8 mL), add acetic anhydride (0.980 mL, 10.36 mmol) dropwise and pyridine (0.980 mL, 10.36 mmol), stir under nitrogen at room temperature for 14 h. Add 1 M hydrochloric acid and extract with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford the title compound (162 mg, 10% over two steps); MS (ES+): 610 (M+H).

Workup

  1. stirringstir for 30 min
  2. filtrationFilter through celite
  3. washwash the residue with AcOEt
  4. extractionSeparate organic layer, extract aqueous with AcOEt
  5. dry with materialWash organic layer with brine and dry the organic layers over anhydrous magnesium sulfate
  6. filtrationFilter
  7. customremove the solvent under reduced pressure
  8. extractionextract with dichloromethane
  9. dry with materialDry the organic layer over anhydrous sodium sulfate
  10. filtrationfilter
  11. customremove the solvent under reduced pressure
  12. customPurify the residue by flash chromatography
  13. washeluting with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-e90ad436c5f44d99a9d80da60d68c6b7
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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