Ammonium Chloride → (4S)-4-{(2R)-2-[(1R, 7aR)-octahydro-4-trimethylsilyloxy-7a-methyl-1H-inden-1-yl]-propyl}-2-cyclopenten-1-one

Temperature

-78 °C

A 10 ml amount of ether was placed into a 100 ml eggplant-shaped flask and cooled to −78° C., followed by adding 14.3 ml of a hexane solution of t-butyllithium (1.54 mol/liter). A 3.94 g amount of the compound (1-9), (2R)-2-[(1R,7aR)-octahydro-4-trimethylsilyloxy-7a-methyl-1H-inden-1-yl]-iodopropane was dissolved in 10 ml of ether and then added to the above solution which was then stirred at −78° C. for 1 hour. A 2.1 g amount of copper iodide and 5.5 ml of tri(N-butyl)phosphine were dissolved in 10 ml of tetrahydrofuran, the solution was then added to the above reaction solution, then this was stirred at −78° C. for 1 hour. Thereto 2.54 g of (4S)-4-(t-butyldimethylsilyloxy)-2-cyclopenten-1-one dissolved in 10 ml of tetrahydrofuran was added. The solution was then stirred at −40° C. for 2 hours. This was poured into 30 ml of a saturated aqueous solution of ammonium chloride, then extraction was performed by 50 ml, 30 ml of ether. The organic layer was washed 2 times with saturated saline, then was dried over anhydrous sodium sulfate, the desiccant was filtered out, and the solvent was distilled off under reduced pressure to obtain a crude product in an amount of 11.7 g. This was dissolved in 150 ml of dichloromethane, 2 ml of 1,8-diazabicyclo[5.4.0]undecene was added, then the solution was stirred at room temperature over night. Thereto 400 ml of ether was added. This was then washed by a saturated aqueous solution of potassium hydrogensulfate, a saturated aqueous solution of sodium hydrogencarbonate, and saturated saline and was dried over anhydrous magnesium sulfate. The desiccant was filtered out, then the solvent was distilled off under reduced pressure to obtain a crude product in an amount of 10.9 g. This was purified by a silica gel column (1R-60, 400 g, hexane/ethyl acetate=40/1, 19/1, 9/1) to obtain the desired product (1-10), (4S)-4-{(2R)-2-[(1R,7aR)-octahydro-4-trimethylsilyloxy-7a-methyl-1H-inden-1-yl]-propyl}-2-cyclopenten-1-one in an amount of 1.76 g (yield 50%).

1. additionadded to the above solution which
2. additionthe solution was then added to the above reaction solution
3. stirringthis was stirred at −78° C. for 1 hour
4. additionwas added
5. stirringThe solution was then stirred at −40° C. for 2 hours
6. extractionextraction
7. washThe organic layer was washed 2 times with saturated saline
8. dry with materialwas dried over anhydrous sodium sulfate
9. filtrationthe desiccant was filtered out
10. distillationthe solvent was distilled off under reduced pressure
11. customto obtain a crude product in an amount of 11.7 g
12. stirringthe solution was stirred at room temperature over night
13. washThis was then washed by a saturated aqueous solution of potassium hydrogensulfate
14. dry with materiala saturated aqueous solution of sodium hydrogencarbonate, and saturated saline and was dried over anhydrous magnesium sulfate
15. filtrationThe desiccant was filtered out
16. distillationthe solvent was distilled off under reduced pressure
17. customto obtain a crude product in an amount of 10.9 g
18. customThis was purified by a silica gel column (1R-60, 400 g, hexane/ethyl acetate=40/1, 19/1, 9/1)

ORD record

ord-46af4a36891e40c7a7ea7e9b629489f2

Source dataset

uspto-grants-2001_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06177586B1