Sodium Hydroxide → 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1H-indol-3-yl]propanoic acid

HRID 1512957Notes

Reaction equation

HRID 1512957 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[C:18]([F:33])=[CH:19][CH:20]=[C:21]4[C:25]=3[NH:24][CH:23]=[C:22]4[CH2:26][CH2:27][C:28]([O:30]CC)=[O:29])[N:13]=2)[CH:5]=[N:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+]>C(O)(C)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[C:18]([F:33])=[CH:19][CH:20]=[C:21]4[C:25]=3[NH:24][CH:23]=[C:22]4[CH2:26][CH2:27][C:28]([OH:30])=[O:29])[N:13]=2)[CH:5]=[N:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 59146095Ethyl 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1H-indol-3-yl]propanoate

Product 1

HCID 445473213-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1H-indol-3-yl]propanoic acidYield 71.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of ethyl 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1H-indol-3-yl]propanoate (D149) (260 mg) in isopropanol (7 mL) and water (7 mL) was added NaOH (5.5 mL, 0.5 M aq) at room temperature. The reaction suspension was stirred at 90° C. for 2 hours, and the solution turned clear. Isopropanol was removed in vacuo and water (8 mL) was added to the residue. The aqueous solution was acidified to pH=1 and extracted with ethyl acetate (3×10 mL). The combined organic phase was dried over sodium sulphate. The organic solution was concentrated and purified by MDAP to afford 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1H-indol-3-yl]propanoic acid (E107) (174 mg) as a white solid. δH (DMSO-d6, 400 MHz): 1.34 (6H, d), 2.57 (2H, t), 2.92 (2H, t), 5.40 (1H, m), 7.03 (1H, m), 7.22 (1H, d), 7.74 (1H, m), 8.82 (1H, d), 9.08 (1H, d), 11.04 (1H, s), 12.08 (1H, s). MS (ES): C21H18ClFN4O4 requires 444; found 445.2 (M+H+).

Workup

  1. customIsopropanol was removed in vacuo and water (8 mL)
  2. additionwas added to the residue
  3. extractionextracted with ethyl acetate (3×10 mL)
  4. dry with materialThe combined organic phase was dried over sodium sulphate
  5. concentrationThe organic solution was concentrated
  6. custompurified by MDAP

Sources & evidence

ORD record
ord-4dfeda556c764beeb9ec26d4f31dd513
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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