Hydrochloric Acid → HCID 58903126, compound

HRID 273408Notes

Reaction equation

HRID 273408 reaction equation
[OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][O:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][C:25]([O:27]C)=[O:26])=[CH:19][CH:18]=3)[CH:10]=2)=[C:4]([CH3:29])[CH:3]=1.[CH2:30]([O:37][CH2:38][CH2:39]O)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[OH-].[Na+].Cl>O1CCCC1.C(OCC)(=O)C.CO.C(OCC)C>[CH2:30]([O:37][CH2:38][CH2:39][O:1][C:2]1[CH:3]=[C:4]([CH3:29])[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][O:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[CH:19][CH:18]=3)[CH:10]=2)=[C:6]([CH3:8])[CH:7]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 121412-(Benzyloxy) ethanol2×HCID 13831Tributylphosphine2×HCID 14798Sodium HydroxideHCID 730421,1'-(Azodicarbonyl)dipiperidine2×HCID 57413460HCID 57413460, compound

Product 1

HCID 58903126HCID 58903126, compoundYield 39.8%

Reagents, catalysts & solvents 4

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

Procedure

To a solution of methyl 3-{4-[(4′-hydroxy-2′,6′-dimethylbiphenyl-3-yl)methoxy]phenyl}propanoate (0.50 g, 1.28 mmol), 2-(benzyloxy)ethanol (0.20 mL, 1.41 mmol) and tributylphosphine (0.48 mL, 1.92 mmol) in tetrahydrofuran (10 mL) was added 1,1′-(azodicarbonyl)dipiperidine (0.48 g, 1.92 mmol) at 0° C. with stirring. The reaction mixture was stirred at room temperature for 18 hrs., and an equivalent amount of the aforementioned reagents (2-(benzyloxy)ethanol, tributylphosphine and 1,1′-(azodicarbonyl)dipiperidine) were added at the same temperature and the mixture was further stirred for 18 hrs. Diethyl ether was added to the reaction mixture and insoluble material was filtered off. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=2/1) to give a colorless oil. Then, to a mixture of the oil, methanol (4 mL) and tetrahydrofuran (8 mL) was added 1 N aqueous sodium hydroxide solution (2.6 mL) at room temperature with stirring, and the mixture was stirred at the same temperature for 2 hrs. The reaction mixture was neutralized with 1 N hydrochloric acid, diluted with ethyl acetate, washed with saturated brine, dried and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1-hexane/ethyl acetate=1/2) to give the title compound (0.26 g, yield 39%) as colorless crystals.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 18 hrs
  2. stirringthe mixture was further stirred for 18 hrs
  3. filtrationwas filtered off
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=2/1)
  6. customto give a colorless oil
  7. stirringwith stirring
  8. stirringthe mixture was stirred at the same temperature for 2 hrs
  9. washwashed with saturated brine
  10. customdried
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1-hexane/ethyl acetate=1/2)

Sources & evidence

ORD record
ord-a446ab5ae3a94fb690350493e6d2b9cb
Source dataset
uspto-grants-2008_11
Patent number
US07456218B2

Reaction notes

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