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

HRID 1512933Notes

Reaction equation

HRID 1512933 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[N:24]([CH3:26])[CH:23]=[C:22]4[CH2:27][CH2:28][O:29][CH2:30][C:31]([O:33]CC)=[O:32])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+].Cl>C1COCC1>[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[N:24]([CH3:26])[CH:23]=[C:22]4[CH2:27][CH2:28][O:29][CH2:30][C:31]([OH:33])=[O:32])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 59146091Ethyl({2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}oxy)acetate

Product 1

HCID 44546859({2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}oxy)acetic acidYield 58.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of ethyl ({2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}oxy)acetate (D104) (20 mg) in THF (5 mL) was added aqueous NaOH (2 M, 1 mL). The reaction was stirred at 20° C. for 4 h. The mixture was acidified with aqueous HCl (2 M) to pH 4-5. After concentration, the residue was partitioned between ethyl acetate (25 mL) and water (25 mL). The organic phase was washed with brine (25 mL), dried over anhydrous sodium sulphate and evaporated to give the crude product, which was purified by Mass Directed Auto Prep to afford ({2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}oxy)acetic acid (E79) (11 mg). δH (DMSO-d6, 400 MHz): 1.36 (6H, d), 2.98 (2H, t), 3.63 (3H, s), 3.74 (2H, t), 4.05 (2H, s), 4.89 (1H, m), 7.17 (1H, t), 7.26 (1H, s), 7.44 (2H, m), 7.81 (1H, dd), 8.13 (1H, dd), 8.19 (1H, d), 12.57 (1H, br s). MS (ES): C24H24ClN3O6 requires 469; found 470.2 (M+H+).

Workup

  1. concentrationAfter concentration
  2. customthe residue was partitioned between ethyl acetate (25 mL) and water (25 mL)
  3. washThe organic phase was washed with brine (25 mL)
  4. dry with materialdried over anhydrous sodium sulphate
  5. customevaporated
  6. customto give the crude product, which
  7. customwas purified by Mass Directed Auto Prep

Sources & evidence

ORD record
ord-64220aee35a44032815cb446cc7fe61d
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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