Hydrochloric Acid → 5-Chloro-2-fluoro-4-((4-oxocyclohexyl)oxy)benzoic acid

HRID 1849803Notes

Reaction equation

HRID 1849803 reaction equation
O1[C:5]2([CH2:10][CH2:9][CH:8]([O:11][C:12]3[C:20]([Cl:21])=[CH:19][C:15]([C:16]([OH:18])=[O:17])=[C:14]([F:22])[CH:13]=3)[CH2:7][CH2:6]2)[O:4]CC1.Cl>CC(C)=O.[Cl-].[Na+].O>[Cl:21][C:20]1[C:12]([O:11][CH:8]2[CH2:9][CH2:10][C:5](=[O:4])[CH2:6][CH2:7]2)=[CH:13][C:14]([F:22])=[C:15]([CH:19]=1)[C:16]([OH:18])=[O:17]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 867036854-(1,4-Dioxaspiro[4.5]decan-8-yloxy)-5-chloro-2-fluorobenzoic acid

Product 1

HCID 867036865-Chloro-2-fluoro-4-((4-oxocyclohexyl)oxy)benzoic acidYield 45%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 4-(1,4-dioxaspiro[4.5]decan-8-yloxy)-5-chloro-2-fluorobenzoic acid (2.95 g, 8.92 mmol) in acetone (100 mL) was added 3 M hydrochloric acid (80 mL). The solution was heated to reflux for 17 hours and cooled to ambient temperature. The mixture was diluted with brine (200 mL) and extracted with ethyl acetate (3×150 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to dryness. The residue was purified by column chromatography with a gradient of a solution of 0.2% acetic acid in ethyl acetate and hexanes from 0-50% to afford the title compound as a colorless solid (1.14 g, 45%): 1H NMR (300 MHz, CDCl3) δ 8.07 (d, J=7.6 Hz, 1H), 6.77 (d, J=11.9 Hz, 1H), 4.82 (br s, 1H), 2.81-2.70 (m, 2H), 2.41-2.35 (m, 4H), 2.15-2.03 (m, 2H) (OH not observed); MS (ES−) m/z 285.1, 287.1 (M−1).

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for 17 hours
  3. extractionextracted with ethyl acetate (3×150 mL)
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to dryness
  7. customThe residue was purified by column chromatography with a gradient of a solution of 0.2% acetic acid in ethyl acetate and hexanes from 0-50%

Sources & evidence

ORD record
ord-897044bf85b346299e4bd12275263784
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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