Methanol → 7-Fluoro-1-(2-methoxy-ethyl)-4-trifluoromethoxy-1H-indole-3-carboxylic acid

HRID 1513367Notes

Reaction equation

HRID 1513367 reaction equation
FC(F)(F)[C:3]([C:5]1[C:13]2[C:8](=[C:9]([F:19])[CH:10]=[CH:11][C:12]=2[O:14][C:15]([F:18])([F:17])[F:16])[N:7]([CH2:20][CH2:21][O:22][CH3:23])[CH:6]=1)=[O:4].C[OH:27]>[OH-].[Na+]>[F:19][C:9]1[CH:10]=[CH:11][C:12]([O:14][C:15]([F:17])([F:18])[F:16])=[C:13]2[C:8]=1[N:7]([CH2:20][CH2:21][O:22][CH3:23])[CH:6]=[C:5]2[C:3]([OH:27])=[O:4]

Participants

4

Reactant 2

HCID 887MethanolHCID 461756482,2,2-Trifluoro-1-[7-fluoro-1-(2-methoxy-ethyl)-4-trifluoromethoxy-1H-indol-3-yl]ethanone

Product 1

HCID 461756497-Fluoro-1-(2-methoxy-ethyl)-4-trifluoromethoxy-1H-indole-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 7 (23.4 g, 62.6 mmol) in MeOH (100 mL) and 5 M NaOH (100 mL) is heated at 80° C. overnight. LC/MS indicates that the reaction is complete. The reaction mixture is cooled to rt, and then concentrated in vacuo to remove most of the MeOH. The residue is dissolved in H2O, and then washed with Et2O once. The aqueous layer is slowly acidified to pH ˜2 with conc. HCl. The acidified suspension is extracted with Et2O, and the organic extract is washed with H2O and brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue is suspended in DCM/heptane (10/90). The white powder 8 (19.4 g, 96%) in the suspension is collected by suction filtration and air-dried. 1H NMR (CDCl3) δ 8.02 (s, 1H), 7.15-7.05 (m, 1H), 7.00-6.90 (m, 1H), 4.49 (t, J=5.0 Hz, 2H), 3.75 (t, J=4.9 Hz, 2H), 3.33 (s, 3H); 19F NMR (CDCl3) δ −57.74 (s, 3F), −135.65 (d, J=11.3 Hz, 1F); MS 363 (M+CH3CN+1), 322 (M+1, 100%).

Workup

  1. temperatureThe reaction mixture is cooled to rt
  2. concentrationconcentrated in vacuo
  3. customto remove most of the MeOH
  4. dissolutionThe residue is dissolved in H2O
  5. washwashed with Et2O once
  6. extractionThe acidified suspension is extracted with Et2O
  7. extractionthe organic extract
  8. washis washed with H2O and brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. filtrationThe white powder 8 (19.4 g, 96%) in the suspension is collected by suction filtration
  13. customair-dried

Sources & evidence

ORD record
ord-a272e8845bee49d8b057e1657c98d1f3
Source dataset
uspto-grants-2012_07
Patent number
US08217178B2

Reaction notes

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