Hydrochloric Acid → HCID 44548223, compound

HRID 1512899Notes

Reaction equation

HRID 1512899 reaction equation
C[O:2][C:3]([C@@H:5]1[CH2:7][C@@H:6]1[C:8]1[C:16]2[C:11](=[C:12]([C:17]3[N:21]=[C:20]([C:22]4[CH:27]=[CH:26][C:25]([O:28][CH:29]([CH3:31])[CH3:30])=[C:24]([Cl:32])[CH:23]=4)[O:19][N:18]=3)[CH:13]=[CH:14][CH:15]=2)[N:10]([CH3:33])[CH:9]=1)=[O:4].[OH-].[Na+].Cl>C1COCC1>[Cl:32][C:24]1[CH:23]=[C:22]([C:20]2[O:19][N:18]=[C:17]([C:12]3[CH:13]=[CH:14][CH:15]=[C:16]4[C:11]=3[N:10]([CH3:33])[CH:9]=[C:8]4[C@H:6]3[CH2:7][C@H:5]3[C:3]([OH:4])=[O:2])[N:21]=2)[CH:27]=[CH:26][C:25]=1[O:28][CH:29]([CH3:30])[CH3:31]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 59146097HCID 59146097, compound

Product 1

HCID 44548223HCID 44548223, compoundYield 51.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of cis-methyl-2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]cyclopropanecarboxylate (D65) (40 mg) in THF (5 mL) was added aqueous NaOH (2 M, 1 mL). The reaction was stirred at 60° C. for 4 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 (20 mL). The organic phase was washed with water (25 mL) and saturated 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 cis-2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]cyclopropanecarboxylic acid (E40) (20 mg). δH (DMSO-d6, 400 MHz): 1.31 (1H, m), 1.36 (6H, d), 1.43 (1H, m), 1.72 (1H, m), 2.45 (1H, m), 3.61 (3H, s), 4.88 (1H, m), 7.21 (2H, m), 7.46 (2H, m), 7.82 (1H, dd), 8.12 (1H, dd), 8.19 (1H, d), 12.28 (1H, br s). MS (ES): C24H22ClN3O4 requires 451; found 452.2 (M+H+).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between ethyl acetate (25 mL) and water (20 mL)
  3. washThe organic phase was washed with water (25 mL) and saturated 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-af8ac2ca5b924009b09ae91373a3ad79
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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