Hydrochloric Acid → 3-(6-{5-[6-[(1-methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoic acid

HRID 1512937Notes

Reaction equation

[OH-].[Na+].[CH3:3][CH:4]([O:6][C:7]1[N:12]=[CH:11][C:10]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:26]=[C:25]4[C:21]([C:22]([CH2:27][CH2:28][C:29]([O:31]CC)=[O:30])=[CH:23][NH:24]4)=[CH:20][CH:19]=3)[N:14]=2)=[CH:9][C:8]=1[C:34]([F:37])([F:36])[F:35])[CH3:5].Cl>CC(O)C.O>[CH3:5][CH:4]([O:6][C:7]1[N:12]=[CH:11][C:10]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:26]=[C:25]4[C:21]([C:22]([CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[CH:23][NH:24]4)=[CH:20][CH:19]=3)[N:14]=2)=[CH:9][C:8]=1[C:34]([F:36])([F:37])[F:35])[CH3:3]

Participants

Conditions

Temperature: 70 °C

Procedure

Sodium hydroxide (37 mg) was added to a solution of ethyl 3-(6-{5-[6-[(1-methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate (D109) (300 mg) in iPrOH (10 mL) and water (10 mL). The resulting mixture was heated at 70° C. for 40 mins. Then 0.5 M HCl solution was added until pH was about 6. The solvent was concentrated, and the residue was dissolved in water. The precipitated solid was purified by Mass Directed Auto Prep to afford 3-(6-{5-[6-[(1-methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoic acid (E83) (111 mg) as a white solid. δH (DMSO-d6, 400 MHz): 1.38 (6H, d), 2.61 (2H, t), 2.97 (2H, t), 5.55 (1H, m), 7.34 (1H, d), 7.72 (2H, m), 8.13 (1H, t), 8.63 (1H, d), 9.20 (1H, d), 11.16 (1H, d), 12.05 (1H, br s). MS (ES): C22H19F3N4O4 requires 460; found 461.2 (M+H+).

Workup

concentrationThe solvent was concentrated
dissolutionthe residue was dissolved in water
customThe precipitated solid was purified by Mass Directed Auto Prep

Sources & evidence

ORD record: ord-489ac7577f104877ba7a61e0e2cb883b
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217028B2

Reaction notes

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