p-Bromochlorobenzene → HCID 67501835, compound

HRID 1187761Notes

Reaction equation

HRID 1187761 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=2)[CH2:11][O:10][C:9]1([CH3:23])[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([NH:21][C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)=[CH:19][CH:20]=2)[CH2:11][O:10][C:9]1([CH3:23])[CH3:22])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 7806p-BromochlorobenzeneHCID 10796Cesium carbonateHCID 66705807HCID 66705807, compound

Product 1

HCID 67501835HCID 67501835, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

In a pressure tube, (S)-4-[2-(4-amino-phenyl)-ethyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (0.3 g), 1-bromo-4-chlorobenzene (215 mg) and cesium carbonate (458 mg) were combined with dioxane (3 ml) to give a yellow suspension. The mixture was degassed by bubbling through argon for several minutes. Xantphos (32.5 mg) and tris(dibenzylideneacetone)dipalladium chloroform complex (29.1 mg) were then added and the tube was sealed. The reaction mixture was stirred at 110° C. overnight. The reaction mixture was then cooled to room temperature and concentrated in vacuo. The residue was purified by flash chromatography (SiO2; gradient: 0% to 100% EtOAc in hexane) to afford (S)-4-{2-[4-(4-chloro-phenylamino)-phenyl]-ethyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (228 mg, 57%) as a yellow oil. MS (EI): 432 ({37Cl}M+), 430 ({35Cl}M+H—OH+), 376 ({37Cl}[M−C4H8]+), 374 ({35Cl}[M−C4H8]), 231 ({37Cl}[ClC6H4NHC6H4CH═CH2]+), 229 ({35Cl}[ClC6H4NHC6H4CH═CH2]+), 57 ([C4H9]+).

Workup

  1. customto give a yellow suspension
  2. customThe mixture was degassed
  3. customby bubbling through argon for several minutes
  4. additionXantphos (32.5 mg) and tris(dibenzylideneacetone)dipalladium chloroform complex (29.1 mg) were then added
  5. customthe tube was sealed
  6. temperatureThe reaction mixture was then cooled to room temperature
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (SiO2; gradient: 0% to 100% EtOAc in hexane)

Sources & evidence

ORD record
ord-0df10265f8e74cfab65efee015e1cb24
Source dataset
uspto-grants-2014_03
Patent number
US08673950B2

Reaction notes

Loading…