Ethyl bromoacetate → [7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]acetic acid

HRID 1512890Notes

Reaction equation

HRID 1512890 reaction equation
C[Mg]Br.[Cl:4][C:5]1[CH:6]=[C:7]([C:15]2[O:19][N:18]=[C:17]([C:20]3[CH:21]=[CH:22][CH:23]=[C:24]4[C:28]=3[NH:27][CH:26]=[CH:25]4)[N:16]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH:12]([CH3:14])[CH3:13].Br[CH2:30][C:31]([O:33]CC)=[O:32]>C(OCC)C.C1(C)C=CC=CC=1>[Cl:4][C:5]1[CH:6]=[C:7]([C:15]2[O:19][N:18]=[C:17]([C:20]3[CH:21]=[CH:22][CH:23]=[C:24]4[C:28]=3[NH:27][CH:26]=[C:25]4[CH2:30][C:31]([OH:33])=[O:32])[N:16]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH:12]([CH3:13])[CH3:14]

Participants

6

Reactant 3

HCID 7748Ethyl bromoacetateHCID 591461207-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indoleHCID 178418573HCID 178418573, compound

Product 1

HCID 44548058[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]acetic acid

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To methylmagnesium bromide solution (3 mol/L in diethyl ether, 0.4 mL) stirred under nitrogen at 0° C. was added a solution of 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole (D51) (354 mg) in diethyl ether (5 mL) dropwise. The reaction mixture was stirred at 0° C. for 30 mins. Ethyl bromoacetate (0.13 mL) in toluene (15 mL) was added dropwise. The resulting mixture was stirred at room temperature for 24 h. The reaction mixture was quenched with saturated ammonium chloride solution; the organic layer was separated and the solvent was evaporated off. The residue was dissolved in tetrahydrofuran (5 mL) and sodium hydroxide (40 mg) in water (5 mL) was added. The reaction mixture was stirred at room temperature for 6 hours. Evaporated off the organic solvent, extracted with ether (100 mL), the water layer was separated and acidified with HCl (1 M) to pH around 1. The solid was filtered and purified by Mass Directed Auto Prep to afford [7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]acetic acid (E31) (86 mg) as a yellow solid. δH (DMSO-d6, 400 MHz): 1.37 (6H, d), 3.74 (2H, s), 4.87-4.93 (1H, m), 7.22 (1H, t), 7.40 (1H, d), 7.45 (1H, d), 7.78 (1H, d), 7.95 (1H, d), 8.21 (1H, dd), 8.37 (1H, d), 10.91 (1H, s), 12.19 (1H, br s). MS (ES): C21H18ClN3O4 requires 411; found 412.1 (M+H+).

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 24 h
  2. customThe reaction mixture was quenched with saturated ammonium chloride solution
  3. customthe organic layer was separated
  4. customthe solvent was evaporated off
  5. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  6. additionsodium hydroxide (40 mg) in water (5 mL) was added
  7. stirringThe reaction mixture was stirred at room temperature for 6 hours
  8. customEvaporated off the organic solvent
  9. extractionextracted with ether (100 mL)
  10. customthe water layer was separated
  11. filtrationThe solid was filtered
  12. custompurified by Mass Directed Auto Prep

Sources & evidence

ORD record
ord-0d8abeae76a846beb5fe90c4e70aaab5
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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