Hydrochloric Acid → 2-{4-[(Butyl{6-[4-(trifluoromethyl)phenyl]pyridin-2-yl}amino) methyl]-2-methylphenoxy}-2-methylpropanoic acid

HRID 1269672Notes

Reaction equation

HRID 1269672 reaction equation
[CH2:1]([N:5]([CH2:22][C:23]1[CH:37]=[CH:36][C:26]([O:27][C:28]([CH3:35])([CH3:34])[C:29]([O:31]CC)=[O:30])=[C:25]([CH3:38])[CH:24]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)[N:7]=1)[CH2:2][CH2:3][CH3:4].[OH-].[Na+].Cl>CO.O1CCCC1>[CH2:1]([N:5]([CH2:22][C:23]1[CH:37]=[CH:36][C:26]([O:27][C:28]([CH3:34])([CH3:35])[C:29]([OH:31])=[O:30])=[C:25]([CH3:38])[CH:24]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[CH:13]=[CH:14][C:15]([C:18]([F:20])([F:19])[F:21])=[CH:16][CH:17]=2)[N:7]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 18448411Ethyl 2-{4-[(butyl{6-[4-(trifluoromethyl)phenyl]pyridin-2-yl}amino)methyl]-2-methylphenoxy}-2-methylpropanoate

Product 1

HCID 248858622-{4-[(Butyl{6-[4-(trifluoromethyl)phenyl]pyridin-2-yl}amino) methyl]-2-methylphenoxy}-2-methylpropanoic acidYield 44.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of ethyl 2-{4-[(butyl{6-[4-(trifluoromethyl)phenyl]pyridin-2-yl}amino)methyl]-2-methylphenoxy}-2-methylpropanoate (45 mg, 0.085 mmol) in methanol (1.5 mL) and tetrahydrofuran (1.5 mL) was added 2M NaOH aq. (1 mL). The resulting mixture was heated to 70° C. for 1 h and then stirred at room temperature for 18 h, before heating to 70° C. for a further 4 h. The reaction mixture was allowed to attain room temperature and the solvents removed in vacuo. The residue was acidified with 2M HCl and extracted with EtOAc (2×10 mL). The organic solution was dried (MgSO4) and the solvents removed in vacuo. Purification by aminopropyl SPE (5 g) conditioning the cartridge, loading the compound and washing with methanol before eluting using 10% NH3 in methanol. Evaporation of the methanolic ammonia yielded a white solid, which was treated with 1 M HCl (5 mL) and then extracted into CH2Cl2 (20 mL). The organic extract was dried (Na2SO4) and the solvent removed in vacuo to afford the title compound as a colourless oil (19 mg).

Workup

  1. temperaturebefore heating to 70° C. for a further 4 h
  2. customto attain room temperature
  3. customthe solvents removed in vacuo
  4. extractionextracted with EtOAc (2×10 mL)
  5. dry with materialThe organic solution was dried (MgSO4)
  6. customthe solvents removed in vacuo
  7. customPurification by aminopropyl SPE (5 g) conditioning the cartridge
  8. washwashing with methanol
  9. washbefore eluting
  10. customEvaporation of the methanolic ammonia
  11. customyielded a white solid, which
  12. extractionextracted into CH2Cl2 (20 mL)
  13. extractionThe organic extract
  14. dry with materialwas dried (Na2SO4)
  15. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-08a5fbdf9c3f42e6b17fabf2ad184349
Source dataset
uspto-grants-2007_04
Patent number
US07199239B2

Reaction notes

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