Hydrochloric Acid → 4-[(4-{[3-Methyl-6-(methyloxy)-2-phenyl-1-naphthalenyl]oxy}phenyl)oxy]butanoic acid

HRID 1993013Notes

Reaction equation

HRID 1993013 reaction equation
[CH3:1][C:2]1[C:3]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[C:4]([O:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][CH2:24][C:25]([O:27]CC)=[O:26])=[CH:17][CH:16]=2)[C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([O:12][CH3:13])=[CH:7][CH:6]=2.[OH-].[Na+].Cl>C1COCC1.CCO>[CH3:1][C:2]1[C:3]([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[C:4]([O:14][C:15]2[CH:16]=[CH:17][C:18]([O:21][CH2:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[CH:19][CH:20]=2)[C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([O:12][CH3:13])=[CH:7][CH:6]=2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 68536177Ethyl 4-[(4-{[3-methyl-6-(methyloxy)-2-phenyl-1-naphthalenyl]oxy}phenyl)oxy]butanoate

Product 1

HCID 115031344-[(4-{[3-Methyl-6-(methyloxy)-2-phenyl-1-naphthalenyl]oxy}phenyl)oxy]butanoic acidYield 88%

Reagents, catalysts & solvents 1

HCID 21873804Tetrahydrofuran ethanolSolvent

Conditions

Temperature
70 °C

Procedure

ethyl 4-[(4-{[3-methyl-6-(methyloxy)-2-phenyl-1 naphthalenyl]oxy}phenyl)oxy]butanoate (288) (0.300 g, 0.638 mmol) was dissolved in a 1:1 THF:EtOH (1:1, 30 mL) mixture. To the above mixture was added 1 N NaOH (6.4 mL) at room temperature and heated to 70° C. The reaction mixture was kept at that temperature for 2 h and cooled at RT. Reaction mixture was concentrated under reduced pressure to afford the residue and the residue was acidified with 25% aqueous HCl (30 mL), and then extracted with EtOAc (3×50 mL). The combined organic layer was washed with brine (1×30 mL), dried (Na2SO4), and concentrated under reduced pressure to afford the crude product which was purified by flash SiO2 column chromatography using hexanes:EtOAc (19:1 to 1:1) as an eluent to afford 0.247 g (88%) of the title product (289) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.10 (s, 1H), 7.65 (s, 1H), 7.57 (d, J=9.2 Hz, 1H), 7.30 (d, J=2.4 Hz, 1H), 7.29 (d, J=7.6 Hz, 2H), 7.24 (m, 1H), 7.16 (d, J=8.4 Hz, 2H), 7.05 and 7.03 (dd, J1=9.2 Hz, J2=2.4 Hz, 1H), 6.66 (d, J=9.2 Hz, 2H), 6.47 (d, J=9.2 Hz, 2H), 3.85 (s, 3H), 3.79 (t, J=6.4 Hz, 2H), 2.30 (t, J=7.2 Hz, 2H), 2.16 (s, 3H), 1.83 (quintet, J=6.8 Hz, 2H). LCMS (ESI) m/z 443.18 (M+H)+.

Workup

  1. temperaturecooled at RT
  2. customReaction mixture
  3. concentrationwas concentrated under reduced pressure
  4. customto afford the residue
  5. extractionextracted with EtOAc (3×50 mL)
  6. washThe combined organic layer was washed with brine (1×30 mL)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customto afford the crude product which
  10. customwas purified by flash SiO2 column chromatography

Sources & evidence

ORD record
ord-f62be1c2852048f6b085b757931aca19
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

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