Sodium Hydroxide → 5-(3,5-Bis-trifluoromethyl-benzylamino)-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester

HRID 2353862Notes

Reaction equation

HRID 2353862 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][CH:17]=[CH:18][C:8]1=2)=[O:6])([CH3:3])[CH3:2].[F:19][C:20]([F:34])([F:33])[C:21]1[CH:22]=[C:23]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[CH2:24][NH2:25].[BH4-].[Na+].[OH-].[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:25][CH2:24][C:23]2[CH:26]=[C:27]([C:29]([F:30])([F:31])[F:32])[CH:28]=[C:21]([C:20]([F:19])([F:33])[F:34])[CH:22]=2)[C:9]2[CH:15]=[CH:16][CH:17]=[CH:18][C:8]1=2)=[O:6])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 5210993,5-Bis(trifluoromethyl)benzylamineHCID 4311764Sodium borohydrideHCID 68680367Isopropyl 5-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate

Product 1

HCID 866160625-(3,5-Bis-trifluoromethyl-benzylamino)-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolvent

Procedure

A mixture of 5-Oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (283 mg, 1.14 mmol), 3,5-Bis(trifluoromethyl)benzylamine (304 mg, 1.25 mmol) and titanium(IV) isopropoxide (0.43 ml, 1.43 mmol) was stirred at room temperature for 6 hours. The mixture was diluted with methanol (5 ml) and treated with sodium borohydride (65 mg, 1.71 mmol), then stirred at room temperature for 18 hours. The mixture was treated with 0.1N NaOH (25 ml) and stirred for 10 minutes, then filtered through Celite. The filtered residue washed successively with diethyl ether and dichloromethane. The filtrate was transferred to a separatory funnel and the organic layer was separated, dried (Na2SO4) and concentrated to provide crude 5-(3,5-Bis-trifluoromethyl-benzylamino)-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester, which was elaborated without purification.

Workup

  1. stirringstirred at room temperature for 18 hours
  2. stirringstirred for 10 minutes
  3. filtrationfiltered through Celite
  4. washThe filtered residue washed successively with diethyl ether and dichloromethane
  5. customThe filtrate was transferred to a separatory funnel
  6. customthe organic layer was separated
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-c5ee00e63ac8466fab8c7ec02f300f4b
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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