Sodium Hydroxide → HCID 86616078, compound

HRID 2353950Notes

Reaction equation

HRID 2353950 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]([Cl: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+]>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]([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]=[CH:16][C:17]([Cl:20])=[C:18]([CH3:19])[C:8]1=2)=[O:6])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 5210993,5-Bis(trifluoromethyl)benzylamineHCID 4311764Sodium borohydrideHCID 68679185HCID 68679185, compound

Product 1

HCID 86616078HCID 86616078, compoundYield 57.4%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolvent

Procedure

Inject titanium isopropoxide (0.176 mL, 0.60 mmol) to a mixture of 8-chloro-9-methyl-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (90 mg, 0.30 mmol) and 3,5-bis(trifluoromethyl)benzylamine (137 mg, 0.45 mmol) at room temperature under an atmosphere of nitrogen and stir the solution for 14 h. Add methanol (1.3 mL) and sodium borohydride (28 mg, 0.75 mmol) and stir the mixture under nitrogen at room temperature for 2 h. Add 0.1M NaOH, 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 sodium sulfate. Filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford (+/−)-5-(3,5-Bis-trifluoromethyl-benzylamino)-8-chloro-9-methyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (90 mg, 57%). Add acetyl chloride (0.025 mL, 0.34 mmol) dropwise to a solution of the amine (90 mg, 0.17 mmol) and pyridine (0.025 mL, 0.34 mmol) in dichloromethane (1.2 mL) at 0° C. Stir under nitrogen at room temperature for 1 h 30 min. Add water and extract with dichloromethane. Dry the organic layer over anhydrous magnesium 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 (40 mg, 42%); MS (ES+): 565 (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 sodium sulfate
  6. filtrationFilter
  7. customremove the solvent under reduced pressure
  8. customPurify the residue by flash chromatography
  9. washeluting with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-64325ca47033464ab66babf763d96821
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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