Hydrochloric Acid → 4-(1-(4-fluorophenyl)-1H-indazol-6-yl)butanoic acid

HRID 718747Notes

Reaction equation

HRID 718747 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([CH2:17][CH2:18][CH2:19][C:20]([O:22]CC)=[O:21])[CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[Li+].[OH-].O1CCOCC1.Cl>O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21])[CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 312751,4-DioxaneHCID 86722323ethyl 4-(1-(4-fluorophenyl)-1H-indazol-6-yl)butanoate

Product 1

HCID 867223224-(1-(4-fluorophenyl)-1H-indazol-6-yl)butanoic acidYield 97%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

A mixture of ethyl 4-(1-(4-fluorophenyl)-1H-indazol-6-yl)butanoate (2, R1=4-Fluorophenyl) (17.95 g, 55.0 mmol), LiOH (3.95 g, 165 mmol), 1,4-dioxane (150 mL) and water (30 mL) was warmed in an oil bath heated to about 80° C. for about 16 h. The mixture was cooled to rt then concentrated under reduced pressure to give a solid. The material was dissolved in water (200 mL) then the mixture was acidified to about pH 1 with hydrochloric acid (6 N) (30 mL, 180 mmol). The mixture was extracted twice with EtOAc (150 mL, then 50 mL) then the combined organic solutions were dried over MgSO4, filtered and the filtrate concentrated under reduced pressure to yield 4-(1-(4-fluorophenyl)-1H-indazol-6-yl)butanoic acid (3, R1=4-Fluorophenyl) (15.87 g, 97%); LC/MS, method 3, Rt=2.19 min, MS m/z 299 (M+H)+. 1H NMR (400 MHz, DMSO) δ 12.03 (s, 1H), 8.30 (d, J=0.9 Hz, 1H), 7.84-7.74 (m, 3H), 7.57 (s, 1H), 7.48-7.39 (m, 2H), 7.13 (dd, J=8.3, 1.2 Hz, 1H), 2.79-2.72 (m, 2H), 2.26-2.22 (m, 2H), 1.91-1.81 (m, 2H).

Workup

  1. temperaturewas warmed in an oil bath
  2. temperatureThe mixture was cooled to rt
  3. concentrationthen concentrated under reduced pressure
  4. customto give a solid
  5. extractionThe mixture was extracted twice with EtOAc (150 mL
  6. dry with material50 mL) then the combined organic solutions were dried over MgSO4
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated under reduced pressure

Sources & evidence

ORD record
ord-51e8739cbcbf44c1afd1453d1fe416b9
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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