Example 3
To a solution of compound (A3) (40.0 g, 92.5 mmol) and toluene (311 mL) was added at −10° C. a solution of NaHMDS in THF (93.2 mL, 185 mmol, 2 M) over a period of 7.5 minutes. A slight increase in temperature was observed. The reaction mixture was stirred at −10° C. for 50 minutes. Then the temperature was raised to 5° C. and kept there overnight. The reaction mixture was then allowed reach room temperature, and an aqueous solution of NaCl (160 g, 5% w/w) was added over a period of 5 minutes. The organic phase was separated and evaporated to dryness in vacuum. The residue was stripped with acetone (200 mL), and the residue was mixed with acetone and oxalic acid (8.30 g, 92.2 mmol) and stirred overnight at room temperature. The mixture was then cooled on ice bath for 1 hour and filtered. The filter cake was washed with cold acetone (2×50 mL) twice, broken up and dried in vacuum at 50° C. to yield compound (A4-hemi-oxalate) (35.0 g, 78%) as a powder, exclusively as the cis isomer as determined by 1H NMR analysis.
LC-MS: RT=0.61 minutes, [M+H]+=396.3 m/z.
1H NMR (600 MHz, DMSO-d6) δ 7.07 (s, 1H), 7.03 (s, 1H), 6.06 (s, 2H), 3.73 (br s, 1H), 2.99-3.16 (m, 2H), 2.73-2.90 (m, 4H), 2.43 (br s, 1H), 1.88-1.96 (m, 1H), 1.60-1.80 (m, 3H), 1.45-1.56 (m, 2H), 1.35 (s, 9H), 0.81 (t, J=7.5 Hz, 3H).
