Isopropanol → HCID 178490602, Verbindung

HRID 1508479Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1508479
C1([SiH](C2C=CC=CC=2)Cl)C=CC=CC=1.[Cl-].[In+3].[Cl-].[Cl-].O[C:20]1([C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[CH2:23][CH:22]([C:24]([O:26][CH3:27])=[O:25])[CH2:21]1.CC(O)C>C(Cl)CCl.O>[CH3:35][O:34][C:31]1[CH:30]=[CH:29][C:28]([C@H:20]2[CH2:21][C@H:22]([C:24]([O:26][CH3:27])=[O:25])[CH2:23]2)=[CH:33][CH:32]=1.[CH3:35][O:34][C:31]1[CH:30]=[CH:29][C:28]([C@@H:20]2[CH2:21][C@H:22]([C:24]([O:26][CH3:27])=[O:25])[CH2:23]2)=[CH:33][CH:32]=1

Komponenten

8

Edukt 4

HCID 3776IsopropanolHCID 74206Chloro(diphenyl)silaneHCID 159675indium(III)chlorideHCID 66524942Methyl 3-hydroxy-3-(4-methoxyphenyl)cyclobutanecarboxylate

Produkt 2

HCID 178490602HCID 178490602, VerbindungHCID 178490603HCID 178490603, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

Diphenylchlorosilane (0.806 mL, 3.71 mmol) was added to a mixture of indium(III) chloride (0.021 g, 0.093 mmol) and methyl 3-hydroxy-3-(4-methoxyphenyl)cyclobutanecarboxylate (0.438 g, 1.85 mmol) in dry ClCH2CH2Cl (3.71 mL) under N2. The reaction mixture was stirred at 25° C. for 15 min. The reaction mixture was diluted with water (20 mL) and extracted with Et2O (3×20 mL). The combined extracts were dried (MgSO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Biotage Horizon, 25M, Si, ˜20 mL/min, 100% hexanes for 144 mL, gradient to 20% EtOAc in hexanes over 2394 mL) to afford a mixture of diastereoisomers (0.37 g, 91% yield). The sample was resolved by chiral HPLC (OJ, 20×250 mm, 9 mL/min, 5% i-PrOH in heptanes) to afford in order of elution methyl trans-3-(4-methoxyphenyl)cyclobutanecarboxylate and methyl cis-3-(4-methoxyphenyl)cyclobutanecarboxylate. trans-diastereoisomer: Rf=0.54 (20% EtOAc/hexanes). LCMS calc.=221.12. found=221.15 (M+H)+. 1H NMR (600 MHz, CHCl3): δ 7.66 (d, J=8.4 Hz, 2H); 7.37 (d, J=8.4 Hz, 2H); 4.29 (s, 3H); 4.25 (s, 3H); 4.24-4.15 (m, 1H); 3.67-3.61 (m, 1H); 3.20-3.14 (m, 2H); 2.93-2.87 (m, 2H). cis-diastereoisomer: Rf=0.54 (20% EtOAc/hexanes), 1H NMR (600 MHz, CHCl3): δ 7.68 (d, J=8.4 Hz, 2H); 7.36 (d, J=8.3 Hz, 2H); 4.28 (s, 3H); 4.20 (s, 3H); 3.93-3.84 (m, 1H); 3.63-3.54 (m, 1H); 3.12-3.06 (m, 2H); 2.94-2.86 (m, 2H).

Aufarbeitung

  1. extractionextracted with Et2O (3×20 mL)
  2. dry with materialThe combined extracts were dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customto give the crude product
  5. customThis was purified by flash chromatography (Biotage Horizon, 25M, Si, ˜20 mL/min, 100% hexanes for 144 mL, gradient to 20% EtOAc in hexanes over 2394 mL)
  6. customto afford
  7. additiona mixture of diastereoisomers (0.37 g, 91% yield)

Quellen und Nachweise

ORD-Eintrag
ord-b43bdda1fa5a491488cbf776dad12104
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09221834B2

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