Azobisisobutyronitrile → HCID 68453320, compound

HRID 2353351Notes

Reaction equation

HRID 2353351 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[CH:14][C:15]([CH3:17])=[CH:16][C:10]=3[CH:9]=2)=[CH:4][C:3]=1[C:18]([F:21])([F:20])[F:19].BrN1C(=O)CCC1=O.CC(N=NC(C#N)(C)C)(C#N)C.Cl.[C:43]([O:47][C:48](=[O:52])[CH2:49][CH2:50][NH2:51])([CH3:46])([CH3:45])[CH3:44].[H-].[Na+]>C(Cl)(Cl)(Cl)Cl.CN(C=O)C>[C:43]([O:47][C:48](=[O:52])[CH2:49][CH2:50][NH:51][CH2:17][C:15]1[CH:14]=[CH:13][C:11]2[S:12][C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([C:18]([F:21])([F:19])[F:20])[CH:4]=3)=[CH:9][C:10]=2[CH:16]=1)([CH3:46])([CH3:45])[CH3:44]

Participants

8

Reactant 5

HCID 6547AzobisisobutyronitrileHCID 24758Sodium hydrideHCID 67184N-bromobutanimideHCID 16218890Tert-butyl 3-aminopropanoate hydrochlorideHCID 684517322-[4-Chloro-3-(trifluoromethyl)phenyl]-5-methyl-1-benzothiophene

Product 1

HCID 68453320HCID 68453320, compoundYield 73.7%

Reagents, catalysts & solvents 2

HCID 5943Carbon TetrachlorideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2-(4-chloro-3-trifluoromethylphenyl)-5-methylbenzo[b]-thiophene (0.746 g, 2.28 mmol) in carbon tetrachloride (23 mL) is added N-bromosuccinimide (0.447 g, 2.51 mmol) and 2,2′-azobisisobuyronitrile (AIBN, 0.075 g, 0.46 mmol). The mixture is stirred at 90° C. overnight, and then concentrated. The residue is passed through a pad of silica gel, which is further rinsed with hexanes. The combined organic solution is concentrated in vacuo. The resulting crude product, 5-bromomethyl-2-(4-chloro-3-trifluoromethylphenyl)benzo[b]thiophene, is dissolved in DMF (2 mL) and added to a pre-stirred suspension of β-alanine t-butyl ester hydrochloride (0.828 g, 4.56 mmol) and sodium hydride (0.365 g, 60% dispersion in mineral oil, 9.12 mmol) in DMF (4 mL). The mixture is stirred at room temperature for 4 hours, quenched with water (1 mL) and concentrated in vacuo. The resulting residue is purified by column chromatography (50% to 70% EtOAc/hexanes) to afford 0.79 g (73%) of 3-{[2-(4-chloro-3-trifluoromethylphenyl)benzo[b]thiophene-5-ylmethyl]amino}propionic acid t-butyl ester as a yellow solid.

Workup

  1. concentrationconcentrated
  2. washis further rinsed with hexanes
  3. concentrationThe combined organic solution is concentrated in vacuo
  4. dissolutionThe resulting crude product, 5-bromomethyl-2-(4-chloro-3-trifluoromethylphenyl)benzo[b]thiophene, is dissolved in DMF (2 mL)
  5. stirringThe mixture is stirred at room temperature for 4 hours
  6. customquenched with water (1 mL)
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue is purified by column chromatography (50% to 70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f327b3dab9344977811c2db971e13206
Source dataset
uspto-grants-2010_07
Patent number
US07750021B2

Reaction notes

Loading…