Pyridine → Isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-7-bromo-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 2353913Notes

Reaction equation

HRID 2353913 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]=[C:31]([Br:35])[C:32]([Cl:34])=[CH:33][C:8]1=2)=[O:6])([CH3:3])[CH3:2].N1C=CC=CC=1.[C:42](OC(=O)C)(=[O:44])[CH3:43]>C(OCC)(=O)C>[CH:1]([O:4][C:5]([N:7]1[CH2:13][CH2:12][CH2:11][CH:10]([N:14]([C:42](=[O:44])[CH3:43])[CH2:15][C:16]2[CH:17]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:19]=[C:20]([C:22]([F:25])([F:23])[F:24])[CH:21]=2)[C:9]2[CH:30]=[C:31]([Br:35])[C:32]([Cl:34])=[CH:33][C:8]1=2)=[O:6])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 866160695-(3,5-Bis-trifluoromethyl-benzylamino)-7-bromo-8-chloro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester

Product 1

HCID 59003215Isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-7-bromo-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylateYield 85%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of crude 5-(3,5-Bis-trifluoromethyl-benzylamino)-7-bromo-8-chloro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (1.40 g, 2.38 mmol) and pyridine (5.00 ml) was treated with acetic anhydride (5.00 ml) via dropwise addition. The mixture was stirred at room temperature overnight and then diluted with ethyl acetate (50.0 ml), washed with 1.00N HCl (2×50.0 ml) and brine (3×150 ml). Dried over Na2SO4, filtered and concentrated. Purification by silica gel chromatography (gradient eluent, 0-40% ethyl acetate in hexane) provided the titled compound (1.28 g, 85%) as white foamy solid. MS (ES+): 629, 631 (M+H).

Workup

  1. washwashed with 1.00N HCl (2×50.0 ml) and brine (3×150 ml)
  2. dry with materialDried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography (gradient eluent, 0-40% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-5a2885a0f48e444f9e5e1fa2aa0f2bbf
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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