Isopropanol → HCID 178490602, compound

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence