Resorcinol → 6-Methoxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)-3,4-dihydronaphthalene-2-carboxylic acid

HRID 445226Notes

Reaction equation

HRID 445226 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8]([CH:29]=[O:30])[CH2:7][CH2:6]2.C1(C=CC=C(O)C=1)[OH:32].C1COCC1.Cl([O-])=O.[Na+]>O.C(O)(=O)C.C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]3)=[CH:16][CH:15]=1)=[C:8]([C:29]([OH:32])=[O:30])[CH2:7][CH2:6]2

Participants

8

Reactant 4

HCID 5054ResorcinolHCID 8028TetrahydrofuranHCID 23668197Sodium ChloriteHCID 583385916-Methoxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)-3,4-dihydronaphthalene-2-carbaldehyde

Product 1

HCID 583385566-Methoxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)-3,4-dihydronaphthalene-2-carboxylic acidYield 21.8%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

To a round bottom flask, add 6-methoxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)-3,4-dihydronaphthalene-2-carbaldehyde (3.0 g, 4.34 mmol), resorcinol (531 mg, 4.8 mmol), THF (8 mL), ethanol (8 mL) and acetic acid (0.9 mL). Stir the mixture at 25° C. for 5 min. Add slowly sodium chlorite (1.3 g, 11.2 mmol) in water (8 mL) to the reaction mixture. Stir the mixture at 80° C. for 2 hours. Quench the reaction mixture with ice-water. Add ethyl acetate to the vessel with stirring. Wash the mixture with dilute NaOH three times and discard the organic phase. To the aqueous layer, add water so the pH was adjusted to 5-6. Extract the aqueous layer with ethyl acetate five times and discard the aqueous phase. Dry the organic layer over MgSO4, filter, and concentrate to dryness, which was further purified to give 400 mg of 6-methoxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)-3,4-dihydronaphthalene-2-carboxylic acid. 1HNMR (d-DMSO, 300 MHZ): 9.97 (1H, s) 7.12 (1H, m), 6.86 (5H, m), 6.71 (1H, m), 4.27 (2H, m), 3.73 (3H, s), 4.26 (2H, s), 3.41 (3H, m), 2.82 (2H, m), 2.59 (2H, m), 1.70 (6H, m).

Workup

  1. stirringStir the mixture at 80° C. for 2 hours
  2. customQuench the reaction mixture with ice-water
  3. stirringAdd ethyl acetate to the vessel with stirring
  4. washWash the mixture with dilute NaOH three times
  5. additionTo the aqueous layer, add water so the pH
  6. extractionExtract the aqueous layer with ethyl acetate five times
  7. dry with materialDry the organic layer over MgSO4
  8. filtrationfilter
  9. concentrationconcentrate to dryness, which
  10. customwas further purified

Sources & evidence

ORD record
ord-7da1ce96bfd04a149dcfedb0eef1113a
Source dataset
uspto-grants-2013_07
Patent number
US08476300B2

Reaction notes

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