Hydrochloric Acid → (R)-(4-(benzyloxy)-2',6'-dimethyl-4'-((tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methanol

HRID 2280685Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2280685
Br[C:2]1[C:13]([CH3:14])=[CH:12][C:5]([O:6][C@@H:7]2[CH2:11][CH2:10][O:9][CH2:8]2)=[CH:4][C:3]=1[CH3:15].[C:16](=[O:19])(O)[O-].[Na+].O.Cl.O1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:25]([O:26][C:27]1[CH:28]=[CH:10][C:11]([C:2]2[C:13]([CH3:14])=[CH:12][C:5]([O:6][C@@H:7]3[CH2:11][CH2:10][O:9][CH2:8]3)=[CH:4][C:3]=2[CH3:15])=[CH:7][C:8]=1[CH2:16][OH:19])[C:24]1[CH:12]=[CH:13][CH:2]=[CH:3][CH:4]=1

Komponenten

7

Edukt 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 86697120(R)-3-(4-bromo-3,5-dimethylphenoxy)tetrahydrofuran

Produkt 1

HCID 89701807(R)-(4-(benzyloxy)-2',6'-dimethyl-4'-((tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methanolAusbeute 63,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Katalysator

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

(R)-3-(4-Bromo-3,5-dimethylphenoxy)tetrahydrofuran 35a (731 mg, 2.69 mmol) was dissolved in 20 mL of dioxane, followed by addition of (2-(benzyloxy)-5-(4,4,5,5-tetramethyl-dioxaborolane-2-yl)phenyl)methanol (1.28 g, 3.76 mmol, prepared by a method disclosed in patent application US2011275797) and 4 mL of aqueous sodium bicarbonate solution (855 mg, 8.07 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (98 mg, 0.14 mmol). The reaction solution was heated to 70° C. and stirred for 4 hours. The resulting solution was cooled and poured into 100 mL of water, 1M hydrochloric acid was added dropwise to adjust the pH to 2-3, and extracted with ethyl acetate (30 mL×3). The combined organic extracts were washed with saturated sodium chloride solution (30 mL), dried with anhydrous magnesium sulphate, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with elution system B to obtain the title compound (R)-(4-(benzyloxy)-2′,6′-dimethyl-4′-((tetrahydrofuran-3-yl)oxy)biphenyl-3-yl)methanol 36a (637 mg, yield 63.7%) as a yellow oil.

Aufarbeitung

  1. customprepared by a method
  2. temperatureThe resulting solution was cooled
  3. additionwas added dropwise
  4. extractionextracted with ethyl acetate (30 mL×3)
  5. washThe combined organic extracts were washed with saturated sodium chloride solution (30 mL)
  6. dry with materialdried with anhydrous magnesium sulphate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography with elution system B

Quellen und Nachweise

ORD-Eintrag
ord-bbacf7719aa94bc68b8ff94430f4c193
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09139548B2

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