Butanoic acid, 4-chloro-4-oxo-, ethyl ester → ethyl 4-{7-[5-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl]-1H-indol-3-yl}-4-oxobutanoate

HRID 1512764Notes

Reaction equation

HRID 1512764 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[NH:24][CH:23]=[CH:22]4)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].Cl[C:27](=[O:35])[CH2:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31]>C(Cl)Cl.[Cl-].[Cl-].[Zn+2]>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[NH:24][CH:23]=[C:22]4[C:27](=[O:35])[CH2:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

5

Reactant 2

HCID 84648Butanoic acid, 4-chloro-4-oxo-, ethyl esterHCID 591461207-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole

Product 1

HCID 59146159ethyl 4-{7-[5-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl]-1H-indol-3-yl}-4-oxobutanoateYield 73.4%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred suspension of 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole (D51) (0.5 g) and ZnCl2 (1.0 g) in DCM (50 mL) was added a solution of ethyl 4-chloro-4-oxobutanoate (2.3 g) in DCM (5 mL) dropwise. After stirring at room temperature overnight, the reaction mixture was washed with water and brine. The organic phase was separated and dried over anhydrous sodium sulphate. Filtration and concentration under vacuum afforded the crude product ethyl 4-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]-4-oxobutanoate (D52) as a brown solid (0.5 g). δH (CDCl3, 400 MHz): 1.27 (3H, t), 1.46 (6H, d), 2.68 (2H, t), 2.83 (2H, t), 3.29 (2H, q), 4.73 (1H, m), 7.07 (1H, d), 7.42 (1H, t), 8.06 (1H, s), 8.08 (1H, dd), 8.16 (1H, dd), 8.26 (1H, dd), 8.56 (1H, d), 10.27 (1H, s). MS (ES): C25H24ClN3O5 requires 481; found 482.2 (M+H+).

Workup

  1. washthe reaction mixture was washed with water and brine
  2. customThe organic phase was separated
  3. dry with materialdried over anhydrous sodium sulphate
  4. filtrationFiltration and concentration under vacuum

Sources & evidence

ORD record
ord-12467d278eb94ee99f5900298e8ffeba
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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