Cesium carbonate → methyl (2R)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-methylpropanoate

HRID 1512770Notes

Reaction equation

HRID 1512770 reaction equation
Br[C:2]1[C:10]2[C:5](=[C:6]([C:11]3[N:15]=[C:14]([C:16]4[CH:21]=[CH:20][C:19]([O:22][CH:23]([CH3:25])[CH3:24])=[C:18]([Cl:26])[CH:17]=4)[O:13][N:12]=3)[CH:7]=[CH:8][CH:9]=2)[N:4]([CH3:27])[CH:3]=1.CC(P(C(C)(C)C)C(C)(C)C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+].Br[Zn][CH2:49][C@@H:50]([CH3:55])[C:51]([O:53][CH3:54])=[O:52]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:26][C:18]1[CH:17]=[C:16]([C:14]2[O:13][N:12]=[C:11]([C:6]3[CH:7]=[CH:8][CH:9]=[C:10]4[C:5]=3[N:4]([CH3:27])[CH:3]=[C:2]4[CH2:49][C@@H:50]([CH3:55])[C:51]([O:53][CH3:54])=[O:52])[N:15]=2)[CH:21]=[CH:20][C:19]=1[O:22][CH:23]([CH3:24])[CH3:25]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 591461473-bromo-7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indoleHCID 178501471HCID 178501471, compound

Product 1

HCID 59146133methyl (2R)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-methylpropanoate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 3-bromo-7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indole (D59) (100 mg), tris(1,1-dimethylethyl)phosphane (13 mg), Pd2(dba)3 (41 mg) and Cs2CO3 (30 mg) in THF (5 mL) stirred under nitrogen at room temperature was added a solution of bromo[(2S)-2-methyl-3-(methyloxy)-3-oxopropyl]zinc (1.0 M in THF, 2 mL) in one portion. The reaction mixture was stirred at 60° C. for 1.5 h. The mixture was cooled to room temperature and filtered. The filtrate was partitioned between ethyl acetate (50 mL) and water (50 mL). The organic phase was washed with water, aqueous HCl (2 M) and brine, dried over sodium sulphate and evaporated to afford methyl (2R)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-methylpropanoate (D60) (120 mg). MS (ES): C25H26ClN3O4 requires 467; found 468.2 (M+H+).

Workup

  1. stirringThe reaction mixture was stirred at 60° C. for 1.5 h
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationfiltered
  4. customThe filtrate was partitioned between ethyl acetate (50 mL) and water (50 mL)
  5. washThe organic phase was washed with water, aqueous HCl (2 M) and brine
  6. dry with materialdried over sodium sulphate
  7. customevaporated

Sources & evidence

ORD record
ord-5bb20d42774a48578a70b73b3ed48684
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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