Sodium Hydroxide → 3-(7-{5-[3-chloro-4,5-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoic acid

HRID 1512904Notes

Reaction equation

HRID 1512904 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:20]=[CH:21][CH:22]=[C:23]4[C:27]=3[NH:26][CH:25]=[C:24]4[CH2:28][CH2:29][C:30]([O:32]C)=[O:31])[N:15]=2)[CH:5]=[C:6]([O:11][CH2:12][CH3:13])[C:7]=1[O:8][CH2:9][CH3:10].[OH-].[Na+]>O1CCCC1.CO.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:20]=[CH:21][CH:22]=[C:23]4[C:27]=3[NH:26][CH:25]=[C:24]4[CH2:28][CH2:29][C:30]([OH:32])=[O:31])[N:15]=2)[CH:5]=[C:6]([O:11][CH2:12][CH3:13])[C:7]=1[O:8][CH2:9][CH3:10]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 59146107methyl 3-(7-{5-[3-chloro-4,5-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate

Product 1

HCID 445484073-(7-{5-[3-chloro-4,5-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoic acidYield 20.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of methyl 3-(7-{5-[3-chloro-4,5-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate (D70) (20 mg) in tetrahydrofuran (5 mL) and methanol (5 mL) stirred at 20° C. was added a solution of sodium hydroxide (9 mg) in water (5 mL) in one charge. The reaction mixture was stirred at 20° C. for 4 h. The organic solvent was evaporated off and the mixture was acidified with HCl (1 M) solution to pH around 1. Extracted with EtOAc (60 mL), the organic layer was separated and the organic solvent was evaporated off. The residue was purified by Mass Directed Auto Prep to afford 3-(7-{5-[3-chloro-4,5-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoic acid (E45) (4 mg) as a TFA salt. δH (DMSO-d6, 400 MHz): 1.34 (3H, t), 1.43 (3H, t), 2.63 (2H, t), 3.00 (2H, t), 4.19 (2H, q), 4.27 (2H, q), 7.21 (1H, t), 7.27 (1H, d), 7.80-7.84 (2H, m), 7.95 (1H, d), 8.01 (1H, d), 10.81 (1H, s), 12.09 (1H, br s). MS (ES): C23H22ClN3O5 requires 455; found 456.2 (M+H+).

Workup

  1. additioncharge
  2. customThe organic solvent was evaporated off
  3. extractionExtracted with EtOAc (60 mL)
  4. customthe organic layer was separated
  5. customthe organic solvent was evaporated off
  6. customThe residue was purified by Mass Directed Auto Prep

Sources & evidence

ORD record
ord-a3edafebc9fd4500bb85f50c0ccac293
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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