Water → (R)-ethyl 3-cyclobutyl-3-(3-hydroxyphenyl)propanoate

HRID 1662498Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1662498
[CH:1]1([C@@H:5]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([OH:17])[CH:12]=2)[CH2:6][C:7]([O:9][CH3:10])=[O:8])[CH2:4][CH2:3][CH2:2]1.[CH:18]1([C@H](C2C=CC=C(O)C=2)CC(OC)=O)CCC1.[OH:35][C:36]1[CH:37]=[C:38](B(O)O)[CH:39]=[CH:40][CH:41]=1.O1CCOCC1.O.[CH:52]1(/[CH:56]=[CH:57]/[C:58]([O:60][CH2:61][CH3:62])=[O:59])[CH2:55][CH2:54][CH2:53]1>CCOC(C)=O>[CH:1]1([C@@H:5]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([OH:17])[CH:12]=2)[CH2:6][C:7]([O:9][CH2:10][CH3:18])=[O:8])[CH2:2][CH2:3][CH2:4]1.[CH:52]1([C@H:56]([C:38]2[CH:39]=[CH:40][CH:41]=[C:36]([OH:35])[CH:37]=2)[CH2:57][C:58]([O:60][CH2:61][CH3:62])=[O:59])[CH2:53][CH2:54][CH2:55]1

Komponenten

9

Edukt 6

HCID 962WaterHCID 312751,4-DioxaneHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 57706492(E)-Ethyl 3-cyclobutylacrylateHCID 67429527methyl (3S)-3-cyclobutyl-3-(3-hydroxyphenyl)propanoateHCID 67429925methyl (3R)-3-cyclobutyl-3-(3-hydroxyphenyl)propanoate

Produkt 2

HCID 57707220(R)-ethyl 3-cyclobutyl-3-(3-hydroxyphenyl)propanoateAusbeute 96 %HCID 57707268(S)-ethyl 3-cyclobutyl-3-(3-hydroxyphenyl)propanoate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

Methyl (3S)-3-cyclobutyl-3-(3-hydroxyphenyl)propanoate or methyl (3R)-3-cyclobutyl-3-(3-hydroxyphenyl)propanoate (70). A mixture of 3-hydroxyphenylboronic acid (available from Aldrich) (2.2 g, 16 mmol) and hydroxy[(S)-BINAP]-rhodium(I) dimer (0.24 g, 0.16 mmol) in 1,4-dioxane (10 mL, 3.2 mmol) was sparged with N2. To the mixture were added water (1.0 mL, 3.2 mmol) and (E)-ethyl 3-cyclobutylacrylate 70.C (0.56 mL, 3.2 mmol). The resulting red-brown solution was warmed to 45° C. and stirred for 3 hours (sealed vial). The mixture was cooled to room temperature, diluted with EtOAc, washed with saturated aqueous NaHCO3 and brine, dried (MgSO4), and concentrated. The crude product was purified by silica gel flash chromatography (0-25% EtOAc/hexane) to afford (S)-ethyl 3-cyclobutyl-3-(3-hydroxyphenyl)propanoate or (R)-ethyl 3-cyclobutyl-3-(3-hydroxyphenyl)propanoate 70 as a pale yellow oil (0.77 g, 96%) (92% e.e.). The enantiomerically enriched mixture was further purified by chiral HPLC (Chiralcel OD, 3% i-PrOH/hexane, 220 nm) to afford 70 as a colorless oil (>99% e.e.).

Aufarbeitung

  1. customwas sparged with N2
  2. custom(sealed vial)
  3. temperatureThe mixture was cooled to room temperature
  4. washwashed with saturated aqueous NaHCO3 and brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel flash chromatography (0-25% EtOAc/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-d94819da3f9645e1bf30120f49801ce2
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08030354B2

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