Trifluoroacetic acid → 2-(3-(2-Hydroxyacetyl)-1H-indazol-1-yl)acetic acid

HRID 1527276Notes

Reaction equation

HRID 1527276 reaction equation
[C:1]([C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]([CH2:13][C:14]([OH:16])=[O:15])[N:5]=1)(=[O:3])[CH3:2].C(O)(C(F)(F)F)=[O:18].FC(F)(F)C(OC1C(OC(=O)C(F)(F)F)=C(I)C=CC=1)=O>CC#N.O>[OH:18][CH2:2][C:1]([C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]([CH2:13][C:14]([OH:16])=[O:15])[N:5]=1)=[O:3]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12041285BistrifluoroacetoxyiodobenzeneHCID 682847152-(3-Acetyl-1H-indazol-1-yl)acetic acid

Product 1

HCID 682837222-(3-(2-Hydroxyacetyl)-1H-indazol-1-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

The title compound was prepared in a similar manner as described by N. Yoshikawa et al., J. Org. Chem., 2002, 67, 2556-2565: A mixture of 2-(3-acetyl-1H-indazol-1-yl)acetic acid (100 mg, 0.46 mmol), TFA (0.71 mL, 0.92 mmol) and bis-(trifluoroacetoxy)-iodobenzene (394 mg, 0.92 mmol) in CH3CN (4 mL) and water (0.6 mL) was heated to reflux (90° C.) for 16 h. Solvents were evaporated and the crude product was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA) to give after lyophilization of the purified fractions the title compound. MS (LC-MS): 233 [M+H]+; tR (HPLC conditions k): 2.41 min.

Workup

  1. customThe title compound was prepared in a similar manner
  2. temperaturewas heated
  3. customSolvents were evaporated
  4. customthe crude product was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA)

Sources & evidence

ORD record
ord-ea5632ca86c94bb49fc12aa51cc33a4d
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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