p-Bromochlorobenzene → (S)-1-(4-Chloro-phenyl)-azepane-2-carboxylic acid

HRID 336220Notes

Reaction equation

HRID 336220 reaction equation
Cl.C(C1ON=C(N[C:12]([C@@H:14]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][NH:15]2)=[O:13])C=1)(C)(C)C.Br[C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=1.C(=O)([O-])[O-:30].[K+].[K+]>CC(N(C)C)=O.CCOC(C)=O.[Cu]I>[Cl:28][C:25]1[CH:26]=[CH:27][C:22]([N:15]2[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C@H:14]2[C:12]([OH:13])=[O:30])=[CH:23][CH:24]=1

Participants

7

Reactant 3

HCID 7806p-BromochlorobenzeneHCID 11430Potassium CarbonateHCID 86660403(S)-Perhydro-azepine-2-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide hydrochloride

Product 1

HCID 58563924(S)-1-(4-Chloro-phenyl)-azepane-2-carboxylic acid

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

A solution of (S)-perhydro-azepine-2-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide hydrochloride (prepared according to Method T, step 6) (0.60 g, 4.20 mmol), 1-Bromo-4-chloro-benzene (0.80 g, 4.20 mmol), potassium carbonate (0.87 g, 6.29 mmol) and copper (I) iodide (0.08 g, 0.42 mmol) in DMA (10.0 mL), is heated at 100° C. in a sealed tube for 48 hours. The reaction mixture is diluted with EtOAc and washed with water. The water phase is acidified with 1N HCl and then extracted with EtOAc. The organic layers are combined, and after drying over anhydrous Na2SO4, removal of the solvent affords the title product that is used in the next step without any further purification. m/z 254 [M+H].

Workup

  1. washwashed with water
  2. extractionextracted with EtOAc
  3. dry with materialafter drying over anhydrous Na2SO4, removal of the solvent

Sources & evidence

ORD record
ord-71e0d94af9a546b5a506860ac50e7d16
Source dataset
uspto-grants-2014_11
Patent number
US08889670B2

Reaction notes

Loading…