Hydrochloric Acid → 7-(isobutylamino)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid

HRID 855094Notes

Reaction equation

HRID 855094 reaction equation
[CH2:1]([NH:5][C:6]1[CH:15]=[C:14]2[C:9]([CH:10]=[C:11]([C:20]([O:22]CC)=[O:21])[CH:12]([C:16]([F:19])([F:18])[F:17])[O:13]2)=[CH:8][CH:7]=1)[CH:2]([CH3:4])[CH3:3].[OH-].[Na+].Cl>C1COCC1.C(O)C.O>[CH2:1]([NH:5][C:6]1[CH:15]=[C:14]2[C:9]([CH:10]=[C:11]([C:20]([OH:22])=[O:21])[CH:12]([C:16]([F:19])([F:17])[F:18])[O:13]2)=[CH:8][CH:7]=1)[CH:2]([CH3:4])[CH3:3]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 69517717ethyl 7-(isobutylamino)-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Product 1

HCID 589348467-(isobutylamino)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acidYield 21%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

The ethyl 7-(isobutylamino)-2-(trifluoromethyl)-2H-chromene-3-carboxylate (0.53 g, 1.54 mmole) was dissolved in a mixture of THF (5.0 mL) and ethanol (5.0 mL). 2.5N sodium hydroxide (1.54 mL) was added and the reaction was heated to 55° C. (oil bath) for 3 hours. The reaction was cooled to room temperature and stirred for 18 hours. The solution was condensed in vacuo to give a yellow oil. The oil was redissolved in water (20 mL), acidified with 2.4 N HCl to pH around 1 and extracted with EtOAc (2×20 mL). The combined extracts were washed with brine (20 mL), dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil which was subject to prep HPLC (reverse phase) and eluted with 50-95% ACN/ water with 0.05% TFA to give a yellow solid (0.1 g, 21%). ESHRMS m/z 314.1023 (M−H, C15H15O3F3N, Calc'd 314.0999). 1H NMR (CDCl3/400 MHz) 7.78 (s, 1H), 7.01 (s, 1H), 6.24 (s, 2H), 5.60 (q, 1H, J=7.0 Hz), 2.97 (m, 2H), 1.91 (m, 1H), 0.98 (m, 6H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customcondensed in vacuo
  3. customto give a yellow oil
  4. extractionextracted with EtOAc (2×20 mL)
  5. washThe combined extracts were washed with brine (20 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a yellow oil which
  10. washeluted with 50-95% ACN/ water with 0.05% TFA

Sources & evidence

ORD record
ord-bc1bed79fa3d4bf0ae1b1bb4be5bcfde
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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