48% |
With diethylzinc; trifluoroacetic acid In dichloromethane at 0 - 20℃; for 1.5h; |
1.5 Preparation of (1R,3r,5S)-bicyclo[3.1.0]hexan-3-ol
Diethyl zinc (7.16 L, 7.14 mol) was added dropwise to methylene chloride (9 L) at 0° C. When the white fume disappeared after the completion of dropwise addition, to the resulting mixture was slowly added dropwise a solution of trifluoroacetic acid (816 g, 7.16 mol) in methylene chloride (1 L). After the completion of dropwise addition, the resulting mixture was stirred for 30 mins. To the mixture was added dropwise a solution of methylene iodide (1918 g, 7.14 mol) in methylene chloride (1 L). After the completion of dropwise addition, the resulting mixture was stirred for 30 mins. To the mixture was added dropwise a solution of cyclopent-3-en-1-ol (200 g, 2.38 mol) in methylene chloride (800 mL). After the completion of dropwise addition, the resulting mixture was warmed up to room temperature and reacted for 30 mins. TLC indicated the completion of reaction. The reaction mixture was poured into a saturated ammonium chloride. After stirring for 10 mins, the mixture was separated into an organic phase and an aqueous phase. The aqueous phase was extracted with methylene chloride (2 L) for one time. The organic phase was washed with a saturated sodium sulphite, with a saturated sodium bicarbonate, and with a saturated sodium chloride, and dried over anhydrous sodium sulphate. The residue is purified with a column chromatography to produce 112 g of a product in a yield of 48%. |
48% |
Stage #1: diiodomethane With diethylzinc; trifluoroacetic acid In dichloromethane at 0℃; for 0.5h;
Stage #2: cyclopent-3-enol In dichloromethane at 0 - 20℃; for 0.5h; |
1.5 (5) Preparation of (1R,3r,5S)-bicyclo[3.1.0]hexan-3-ol
Diethyl zinc (7.16L, 7.14mol) was added dropwise to methylene chloride (9L) at 0°C. When the white fume disappeared after the completion of dropwise addition, to the resulting mixture was slowly added dropwise a solution of trifluoroacetic acid (816g, 7.16mol) in methylene chloride (1L). After the completion of dropwise addition, the resulting mixture was stirred for 30mins. To the mixture was added dropwise a solution of methylene iodide (1918g, 7.14mol) in methylene chloride (1L). After the completion of dropwise addition, the resulting mixture was stirred for 30mins. To the mixture was added dropwise a solution of cyclopent-3-en-1-ol (200g, 2.38mol) in methylene chloride (800mL). After the completion of dropwise addition, the resulting mixture was warmed up to room temperature and reacted for 30mins. TLC indicated the completion of reaction. The reaction mixture was poured into a saturated ammonium chloride. After stirring for 10mins, the mixture was separated into an organic phase and an aqueous phase. The aqueous phase was extracted with methylene chloride (2L) for one time. The organic phase was washed with a saturated sodium sulphite, with a saturated sodium bicarbonate, and with a saturated sodium chloride, and dried over anhydrous sodium sulphate. The residue is purified with a column chromatography to produce 112g of a product in a yield of 48%. |
48% |
Stage #1: diiodomethane With diethylzinc; trifluoroacetic acid In dichloromethane at 0℃; for 1h;
Stage #2: cyclopent-3-enol In dichloromethane at 20℃; for 0.5h; |
1.5 (5) Preparation of -(1R, 3r, 5S)bicyclo [3.1.0] hexane-3-ol
Diethyl zinc (7.16 L, 7.14 mol) was added to a solution ofWas added dropwise to methylene chloride (9 L) at 0 ° C.When the white vapor disappears after completion of the dropping,To the resulting mixture was added methylene chloride (1 L)A solution of triflu or o acetic acid (816 g, 7.16 mol) was slowly added dropwise.After completion of the dropwise addition, the resulting mixture was stirred for 30 minutes.To the mixture was added methylene chloride (1 L)A solution of methylene iodide (1918 g, 7.14 mol) was added dropwise. After completion of the dropwise addition, the resulting mixture was stirred for 30 minutes.To this mixture was added dropwise a solution of cyclopent-3-en-1-ol (200 g, 2.38 mol) in methylene chloride (800 mL).After completion of the dropwise addition, the resulting mixture was allowed to warm to room temperature and reacted for 30 minutes.TLC indicated completion of the reaction. The reaction mixture was poured into saturated ammonium chloride. After stirring for 10 minutes, the mixture was separated into an organic phase and an aqueous phase. The aqueous phase was extracted once with methylene chloride (2 L). The organic phase was washed with saturated sodium sulphite, saturated sodium bicarbonate, and saturated sodium chloride and dried over anhydrous sodium sulfate. The residue was purified by column chromatography to give 112 g of product in 48% yieldAll. |