CIS-ZHPROME

To a mixture of benzyl chloroformate (3.7 mL, 26.3 mmol) and potassium carbonate (10.6 g, 76.7 mmol) in a mixed solvent of THF and H20 (THF/H20 (v/v) = 20 mL/10 mL) was added compound 19-3 (3.1 g, 17.1 mmol) in one portion with vigorous stirring. At the end of the addition, the mixuture was stirred at rt overnight. After the reaction was completed, the mixture was acidified with aqueous HC1 (1 M) till pH = 1 and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with a saturated aqueous solution of NaCl, dried over anhydrous Na2S04 and concentrated in vacuo. The residue was purified by silica gel column chromatography (PE/EtOAc (v/v) = 4/1) to give the title compound as pale yellow oil (3 g, 62.8percent). The compound was characterized by the following spectroscopic data: lli NMR (400 Hz, CDCI3): δ 7.47 (d, 2H, J = 8.24 Hz), 7.38 (d, 2H, J= 8.24 Hz), 7.24 (m, 1H), 5.09 (s, 2H), 4.18 (t, 1H), 3.68 (s, 3H), 3.63 (m, 1H), 3.58 (s, 1H), 3.38 (m, 1H), 3.32 (m, 1H), 2.21 (m, 1H), 1.96 (m, 1H) ppmCompound 15-2 (3.1 g, 17.1 mmol) was added in one portion to a vigorouslystirred mixture of benzyl chloroformate (3.7 mL, 26.3 mmol) and potassium carbonate(10.6 g, 76.7 mmol) in THF / H 2O (20 mL / 10 mL). After the addition was complete, react at room temperature overnight. After the reaction was completed, the reactionmixture was adjusted to pH 3 with dilute hydrochloric acid (1 M) and extracted withEtOAc (50 mL x 3). The organic phases were combined, washed with brine, dried overanhydrous sodium sulfate and concentrated. Separation and purification (eluent: PE /EtOAc (v / v) = 4/1) gave 3.0 g of a pale yellow oily liquid, yield: 62.8percent.To a vigorously stirred solution of benzyl chloroformate (3.7 mL, 26.3 mmol) and KTo a mixture of compound Q-1 (2 g, 15.3 mmol) in CHTo a solution of benzyl chloroformate (3.7 mL, 26.3 mmol) and K2CO3 (10.6 g, 76.7 mmol) in mixed solventsof THF (20 mL) and H2O (10 mL) was added compound Q-2 (3.1 g, 17.1 mmol) in one portion while the mixture wasstirred vigorously. At the end of the addition, the mixture was stirred at rt overnight, adjusted to pH 3 with dilutedhydrochloric acid and extracted with EtOAc (50 mL x 3). The combined organic phases were dried over anhydrousNa2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography(PE/EtOAc (v/v) = 4/1) to give compound Q-3 as pale yellow oil (3 g, 62.8percent). The compound was characterizedby the following spectroscopic data:1H NMR (400 MHz, CD3Cl): δ 7.47 (d, J = 8.24 Hz, 2H), 7.38 (d, J = 8.24 Hz, 2H), 7.24 (m, 1H), 5.09 (s, 2H), 4.18(t, 1H), 3.68 (s, 3H), 3.63 (m, 1H), 3.58 (s, 1H), 3.38 (m, 1H), 3.32 (m, 1H), 2.21 (m, 1H), 1.96 (m, 1H).To a solution of D (23 g, 65.8 mmol) in MeOH (100 mL) was added K