Hydrochloric Acid → 3-{4-[(4-{[4-(2,6-Diisopropylphenoxy)piperidin-1-yl]methyl}benzyl)oxy]phenyl}propanoic acid

HRID 2110886Notes

Reaction equation

HRID 2110886 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:28]=[CH:27][C:12]([CH2:13][O:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][C:23]([O:25]C)=[O:24])=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.[CH:29]([C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH:38]([CH3:40])[CH3:39])[C:33]=1O)([CH3:31])[CH3:30].C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[OH-].[Na+].Cl>C(OCC)(=O)C.O1CCCC1.CO.C(OCC)C>[CH:38]([C:34]1[CH:35]=[CH:36][CH:37]=[C:32]([CH:29]([CH3:31])[CH3:30])[C:33]=1[O:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([CH2:13][O:14][C:15]3[CH:16]=[CH:17][C:18]([CH2:21][CH2:22][C:23]([OH:25])=[O:24])=[CH:19][CH:20]=3)=[CH:27][CH:28]=2)[CH2:4][CH2:3]1)([CH3:40])[CH3:39]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 4943PropofolHCID 13831TributylphosphineHCID 14798Sodium HydroxideHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 23159986Methyl 3-[4-({4-[(4-hydroxypiperidin-1-yl)methyl]benzyl}oxy)phenyl]propanoate

Product 1

HCID 231599393-{4-[(4-{[4-(2,6-Diisopropylphenoxy)piperidin-1-yl]methyl}benzyl)oxy]phenyl}propanoic acidYield 16.3%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of methyl 3-[4-({4-[(4-hydroxypiperidin-1-yl)methyl]benzyl}oxy)phenyl]propanoate (0.20 g, 0.52 mmol), 2,6-diisopropylphenol (0.15 mL, 0.78 mmol), tributylphosphine (0.20 mL, 0.78 mmol) and tetrahydrofuran (6.0 mL) was added 1,1′-(azodicarbonyl)dipiperidine (0.20 g, 0.78 mmol) with stirring at 0° C., and the mixture was stirred at room temperature for 16 hr. Diethyl ether was added to the reaction mixture, the insoluble material was filtered off, and the filtrate was concentrated under reduced pressure to give an oil. Then, a mixture of the obtained oil, 1 N aqueous sodium hydroxide solution (1.0 mL), methanol (3.0 mL) and tetrahydrofuran (6.0 mL) was stirred at room temperature for 2 hr. The reaction mixture was neutralized with 1 N hydrochloric acid, and diluted with ethyl acetate. The mixture washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1-hexane/ethyl acetate=1/2) to give the title compound (45 mg, yield 16%) as colorless crystals. MS (APCI−): 528 (M−H).

Workup

  1. stirringthe mixture was stirred at room temperature for 16 hr
  2. filtrationthe insoluble material was filtered off
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customto give an oil
  5. stirringwas stirred at room temperature for 2 hr
  6. washThe mixture washed with water and saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1-hexane/ethyl acetate=1/2)

Sources & evidence

ORD record
ord-35ffaea458a046dd8310fcb25c13e7dc
Source dataset
uspto-grants-2009_04
Patent number
US07517910B2

Reaction notes

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