Hydrochloric Acid → HCID 44548221, compound

HRID 1512896Notes

Reaction equation

HRID 1512896 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/[CH:27]=[CH:28]/[C:29]([O:31]CC)=[O:30])[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/[CH:27]=[CH:28]/[C:29]([OH:31])=[O:30])[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 59146049HCID 59146049, compound

Product 1

HCID 44548221HCID 44548221, compoundYield 79.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of ethyl (2E)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-propenoate (D62) (40 mg) in THF (5 mL) was added aqueous NaOH (2 M, 1 mL). The reaction was stirred at 60° C. for 24 h. The mixture was cooled to room temperature and acidified with aqueous HCl (2 M) to pH 4-5, partitioned between ethyl acetate (25 mL) and water (25 mL). The organic phase was washed with water (25 mL) and 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 (2E)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-propenoic acid (E37) (30 mg). δH (DMSO-d6, 400 MHz): 1.35 (6H, d), 3.70 (3H, s), 4.89 (1H, m), 6.38 (1H, d), 7.35 (1H, t), 7.45 (1H, d), 7.53 (1H, d), 7.81 (1H, d), 8.02 (1H, s), 8.14 (2H, m), 8.21 (1H, d), 12.04 (1H, br s). MS (ES): C23H20ClN3O4 requires 437. found 438.2 (M+H+).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between ethyl acetate (25 mL) and water (25 mL)
  3. washThe organic phase was washed with water (25 mL) and 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-ff4b297005a54b7f95628dcb84782b91
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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