Pyridine → 5-[Acetyl-(3,5-bistrifluoromethylbenzyl)amino]-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylic acid isopropyl ester

HRID 2353863Notes

Reaction equation

HRID 2353863 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:13][CH2:12][CH2:11][CH:10]([NH:14][CH2:15][C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=2)[C:9]2[CH:30]=[CH:31][CH:32]=[CH:33][C:8]1=2)=[O:6])([CH3:3])[CH3:2].N1C=CC=CC=1.[C:40](OC(=O)C)(=[O:42])[CH3:41].[OH-].[Na+]>ClCCl>[CH:1]([O:4][C:5]([N:7]1[CH2:13][CH2:12][CH2:11][CH:10]([N:14]([C:40](=[O:42])[CH3:41])[CH2:15][C:16]2[CH:21]=[C:20]([C:22]([F:24])([F:25])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:27])[F:28])[CH:17]=2)[C:9]2[CH:30]=[CH:31][CH:32]=[CH:33][C:8]1=2)=[O:6])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 14798Sodium HydroxideHCID 866160625-(3,5-Bis-trifluoromethyl-benzylamino)-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester

Product 1

HCID 113413065-[Acetyl-(3,5-bistrifluoromethylbenzyl)amino]-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylic acid isopropyl esterYield 66.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of crude 5-(3,5-Bis-trifluoromethyl-benzylamino)-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (200 mg, 0.42 mmol) and pyridine (0.85 ml, 10.5 mmol) in dichloromethane (2 ml) at room temperature was treated with acetic anhydride (0.79 ml, 8.4 mmol) via dropwise addition over 4 minutes. The mixture was stirred at room temperature for 20 hours. The mixture was cooled (0° C.) and treated with 1N NaOH and stirred for 30 minutes. The aqueous layer was extracted with dichloromethane. The combined organic phases were washed with 1N HCl, dried (Na2SO4) and concentrated to an oil. Purification by silica gel chromatography (eluent, 2:1 n-hexanes:ethyl acetate) provided 5-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (144 mg).

Workup

  1. temperatureThe mixture was cooled (0° C.)
  2. stirringstirred for 30 minutes
  3. extractionThe aqueous layer was extracted with dichloromethane
  4. washThe combined organic phases were washed with 1N HCl
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated to an oil
  7. customPurification by silica gel chromatography (eluent, 2:1 n-hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-ee1f8bf97f4846bfb93f9ff3fbdf5355
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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