Cesium fluoride → 5-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-8-chloro-7-methyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester

HRID 2353914Notes

Reaction equation

HRID 2353914 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:13][CH2:12][CH2:11][CH:10]([N:14]([C:30](=[O:32])[CH3:31])[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:33]=[C:34](Br)[C:35]([Cl:37])=[CH:36][C:8]1=2)=[O:6])([CH3:3])[CH3:2].[CH3:39]B(O)O.[F-].[Cs+]>O1CCOCC1>[CH:1]([O:4][C:5]([N:7]1[CH2:13][CH2:12][CH2:11][CH:10]([N:14]([C:30](=[O:32])[CH3:31])[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:33]=[C:34]([CH3:39])[C:35]([Cl:37])=[CH:36][C:8]1=2)=[O:6])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 139377Methylboronic AcidHCID 59003215Isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-7-bromo-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

Product 1

HCID 590031855-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-8-chloro-7-methyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl esterYield 77.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-7-bromo-8-chloro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (0.118 g, 0.187 mmol), methyl boronic acid (0.0340 g, 0.561 mmol) and cesium fluoride (0.0990 mg, 0.655 mmol) in dioxane (2.00 ml) was purged with nitrogen for 10 minutes. To it was added PdCl2(dppf) (0.0240 g) in one portion. The mixture was heated at 100° C. overnight. The solid was removed by filtration, washed with ethyl acetate (30.0 ml) and the filtrate was concentrated in vacuo. Purification by silica gel chromatography (gradient eluent, 0-35% ethyl acetate in hexane) provided the titled compound (0.0820 g, 77%) as white foamy solid. MS (ES+): 565 (M+H).

Workup

  1. customwas purged with nitrogen for 10 minutes
  2. additionTo it was added PdCl2(dppf) (0.0240 g) in one portion
  3. customThe solid was removed by filtration
  4. washwashed with ethyl acetate (30.0 ml)
  5. concentrationthe filtrate was concentrated in vacuo
  6. customPurification by silica gel chromatography (gradient eluent, 0-35% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-c722412fe7bf4b8a9b3b3efe082cfa2c
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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