Hydrochloric Acid → [8-Fluoro-2-isopropyl-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-yloxy]acetic acid

HRID 1944365Notes

Reaction equation

HRID 1944365 reaction equation
C[O:2][C:3](=[O:33])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([CH3:32])=[C:9]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]3[CH:31]=[CH:30][CH:29]=[N:28]3)=[CH:23][CH:22]=1)[C:10]([CH:17]([CH3:19])[CH3:18])=[N:11]2.[OH-].[Li+].Cl>O1CCCC1.O>[F:16][C:13]1[CH:14]=[CH:15][C:6]([O:5][CH2:4][C:3]([OH:33])=[O:2])=[C:7]2[C:12]=1[N:11]=[C:10]([CH:17]([CH3:18])[CH3:19])[C:9]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]3[CH:31]=[CH:30][CH:29]=[N:28]3)=[CH:23][CH:22]=1)=[C:8]2[CH3:32]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium Hydroxide2×HCID 67456367[8-Fluoro-2-isopropyl-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-yloxy]acetic acid methyl ester

Product 1

HCID 25097594[8-Fluoro-2-isopropyl-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-yloxy]acetic acidYield 25%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of [8-fluoro-2-isopropyl-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-yloxy]acetic acid methyl ester (0.062 g) in tetrahydrofuran (0.70 mL) and water (0.70 mL) was treated with lithium hydroxide (0.033 g), and the resulting mixture was stirred at room temperature. After 24 hours, the mixture was treated with additional lithium hydroxide (0.033 g) and stirring continued for 16 hours. The mixture was cooled to 0° C., acidified with 1.0 M aqueous hydrochloric acid and extracted with ethyl acetate (3×5.0 mL). The combined extracts were washed with saturated aqueous sodium chloride solution (2.0 mL), dried over magnesium sulfate and concentrated under reduced pressure. Purification of the residue by preparative reverse-phase HPLC, eluting with a mixture of acetonitrile and water (40:60 to 19:1 by volume) gave title compound as a yellow solid (0.015 g).

Workup

  1. stirringstirring
  2. waitcontinued for 16 hours
  3. temperatureThe mixture was cooled to 0° C.
  4. extractionextracted with ethyl acetate (3×5.0 mL)
  5. washThe combined extracts were washed with saturated aqueous sodium chloride solution (2.0 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customPurification of the residue by preparative reverse-phase HPLC
  9. washeluting with a mixture of acetonitrile and water (40:60 to 19:1 by volume)

Sources & evidence

ORD record
ord-c836833a48ac4ada933941bf14947936
Source dataset
uspto-grants-2013_03
Patent number
US08394830B2

Reaction notes

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