Hydrochloric Acid → HCID 69316359, compound

HRID 273412Notes

Reaction equation

HRID 273412 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.[CH3:30][C:31]1[N:36]=[C:35]([CH2:37]O)[CH:34]=[CH:33][CH:32]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.[OH-].[Na+].[ClH:74].C(OCC)(=O)C.Cl>O1CCCC1.C(OCC)(=O)C.CO>[ClH:74].[CH3:8][C:6]1[CH:7]=[C:2]([O:1][CH2:37][C:35]2[CH:34]=[CH:33][CH:32]=[C:31]([CH3:30])[N:36]=2)[CH:3]=[C:4]([CH3:29])[C:5]=1[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][O:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[CH:19][CH:18]=2)[CH:10]=1

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 11776Triphenylphosphine2×HCID 14798Sodium HydroxideHCID 707366-Methyl-2-pyridylmethanol2×HCID 75555Diisopropyl diazene-1,2-dicarboxylate2×HCID 21866389Hydrogen chloride-ethyl acetateHCID 57413460HCID 57413460, compound

Product 1

HCID 69316359HCID 69316359, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of methyl 3-{4-[(4′-hydroxy-2′,6′-dimethylbiphenyl-3-yl)methoxy]phenyl}propanoate (0.40 g, 1.03 mmol), (6-methylpyridin-2-yl)methanol (0.14 g, 1.13 mmol) and triphenylphosphine (0.34 g, 1.31 mmol) in tetrahydrofuran (8.0 mL) was added diisopropyl azodicarboxylate (40% toluene solution, 0.59 mL, 1.13 mmol) at room temperature with stirring. The reaction mixture was stirred at room temperature for 12 hrs., and an equivalent amount of the aforementioned reagents ((6-methylpyridin-2-yl)methanol, triphenylphosphine and diisopropyl azodicarboxylate) were added and the mixture was further stirred at the same temperature for 12 hrs. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=1/1) 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 (2.1 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=10/1-hexane/ethyl acetate=1/4) to give a colorless oil. The oil was dissolved in ethyl acetate and 4 N hydrogen chloride-ethyl acetate solution was added. The mixture was concentrated under reduced pressure. The obtained crystals were collected by filtration, washed and dried to give the title compound (0.24 g, yield 44%) as colorless crystals.

Workup

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

Sources & evidence

ORD record
ord-b00bf4852b334ff983aa54f60303cd16
Source dataset
uspto-grants-2008_11
Patent number
US07456218B2

Reaction notes

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