methyl (1R,5S)-6-oxabicyclo[3.1.0]hexane-3-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl (1S,5R)-6-oxabicyclo[3.1.0]hexane-3-carboxylate (300 mg, 2.110 mmol) in 3 ml of dichloroethane in a Teflon tube was added hydrogen fluoride-pyridine (0.190 ml, 2.110 mmol and allowed to stir at ambient for 6 hrs. Carefully poured onto 5 ml ice/NaHCO3 and extracted with three portions of DCM. Dried over sodium sulfate followed by Silica gel chromatgraphy with 30-50% Acetone-hexane to give title compound. 1H NMR (500 MHz, CDCl3) δ 1.96-2.03 (m, 1H), δ 2.12-2.32 (m, 3H), δ 2.38-2.52 (m, 1H), δ 3.12 (m, 1H), δ 3.72 (s, 3H), δ 4.34 (m, 1H), δ 4.86 (d of m, J=51.5 Hz, 1H) extracted with three portions of DCM Dried over sodium sulfate

Conditions: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of copper(I) iodide (4.95 g, 26.0 mmol) in 50 ml ether at −25° C. was added ethyllithium (1.7M, 30.6 ml, 52.0 mmol) dropwise. The solution was stirred for 1 hr at −25° C. followed by dropwise addition of an ether solution (50 ml) of methyl (1S,5R)-6-oxabicyclo[3.1.0]hexane-3-carboxylate (1.848 g, 13 mmol) maintaining at −25° C. The reaction was allowed to warm to rt until TLC showed complete reaction. Cooled in ice and quenched with NH4Cl (sat)(5 ml) and stirred for 10 minutes. Filtered thru celite and washed with ether (3×10 ml) and the combined filtrates were washed with brine and dryed over sodium sulfate. Silica gel chromatagraphy on a 25 g Biotage SNAP column with 10-50% MTBE/Hexane afforded title compound. 1H NMR (500 MHz, CDCl3) δ 0.96 (t, J=7.3 Hz, 3H), δ 1.24-1.48 (m, 2H), δ 1.54-1.77 (m, 3H), δ 1.83-1.90 (m, 1H), δ 2.12-2.29 (m, 2H), δ 3.02 (m, 1H), δ 3.69 (s, 3H), δ 3.98 (m, 1H) maintaining at −25° C to warm to rt until TLC reaction Cooled in ice quenched with NH4Cl (sat)(5 ml) stirred for 10 minutes Filtered thru celite washed with ether (3×10 ml) the combined filtrates were washed with brine

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl (1S,5R)-6-oxabicyclo[3.1.0]hexane-3-carboxylate (8 g, 56.3 mmol) and tetrabutylammonium bisulfate (1.911 g, 5.63 mmol) were suspended in THF (5 ml) and water (75 ml) and allowed to stir for 48 hrs. Added solid NaCl and extracted with three 250 ml portions of EtOAc. Added 100 ml Hexane washed with brine and dryed over sodium sulfate. Silca gel chromatography on a 50 g Biotage SNAP cartridge with 40-60% acetone-hexane to give title product as a clear oil. 1H NMR (500 MHz, CDCl3) δ 1.89-2.03 (m, 3H), δ 2.26-2.42 (m, 3H), δ 3.08-3.15 (m, 1H), δ 3.74 (s, 3H), δ 4.06 (m, 1H), δ 4.23 (m, 1H) extracted with three 250 ml portions of EtOAc Added 100 ml Hexane washed with brine

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl (1S,5R)-6-oxabicyclo[3.1.0]hexane-3-carboxylate (8 g, 56.3 mmol) in MTBE (100 ml) was hydrogenated at 3 atm on Parr shaker for 12 hrs. Filtered through celite evaporated followed by chromatagraphy on a 50 g silica gel Biotage Snap cartridge with 10-50% 6:3:1 Hexane-MTBE-MeCN/Hexane to give title compound. 1H NMR (500 MHz, CDCl3) δ 1.63-1.74 (m, 3H), δ 1.78 (s, br, 1H), δ 1.82-2.07 (m, 4H), δ 2.11-2.19 (m, 1H), δ 3.09 (m, 1H), δ 3.70 (s, 3H), δ 4.48 (m, 1H) Filtered through celite evaporated