Water → HCID 66902461, compound

Temperature

0 °C

To a solution of ethyl (6S)-4-thiabicyclo[3.1.0]hex-2-ene-6-carboxylate (22.2 g, 131 mmol) in 136 mL of tetrahydrofuran under nitrogen at 0° C. is added borane-THF complex (98 mL, 98 mmol) over 15-20 minutes. After stirring at 0° C. for 30 minutes, the reaction is allowed to warm to 15° C. and stir until complete by HPLC (1.5-2 hours). The reaction is cooled to 0° C. and transferred over 10-15 minutes to 111 mL of a pre-cooled (0° C.) 1 N pH 7 buffer solution while maintaining the temperature at 0° C. To the mixture is added sodium perborate monohydrate (15.6 g, 157 mmol) as a solid in five portions such that the temperature is maintained below 20° C. The solution is allowed to warm to room temperature and stir for 1 hour followed by the addition of 222 mL of water. After stirring for 2 hours, the peroxides are quenched by adding sodium thiosulfate pentahydrate (9.7 g) dissolved in 24 mL of water followed by stirring for 10 minutes. The mixture is extracted with ethyl acetate (2×222 mL). The combined organic extracts are washed with saturated aqueous sodium bicarbonate (1×222 mL) followed by brine (1×222 mL) and concentration in vacuo to dryness. The crude product is dissolved in 1,2-dichloroethane (1 mL per 1 g of crude oil) and loaded onto a silica gel column (4 g of silica gel per 1 g of crude oil slurried and packed in 15% ethyl acetate-heptane). The column is eluted with 15% ethyl acetate-heptane until product is visible by TLC, at which time the solvent is switched to 50% ethyl acetate-heptane. All fractions containing the title product are combined and concentrated in vacuo to an oil. Overall yield is in the 55-65% range.

1. temperatureto warm to 15° C.
2. stirringstir until complete by HPLC (1.5-2 hours)
3. temperatureThe reaction is cooled to 0° C.
4. waittransferred over 10-15 minutes to 111 mL
5. temperaturewhile maintaining the temperature at 0° C
6. temperatureis maintained below 20° C
7. temperatureto warm to room temperature
8. stirringstir for 1 hour
9. stirringAfter stirring for 2 hours
10. customthe peroxides are quenched
11. additionby adding sodium thiosulfate pentahydrate (9.7 g)
12. dissolutiondissolved in 24 mL of water
13. stirringby stirring for 10 minutes
14. extractionThe mixture is extracted with ethyl acetate (2×222 mL)
15. washThe combined organic extracts are washed with saturated aqueous sodium bicarbonate (1×222 mL)
16. concentrationfollowed by brine (1×222 mL) and concentration in vacuo to dryness
17. dissolutionThe crude product is dissolved in 1,2-dichloroethane (1 mL per 1 g of crude oil)
18. washThe column is eluted with 15% ethyl acetate-heptane until product
19. additionAll fractions containing the title product
20. concentrationconcentrated in vacuo to an oil
21. customOverall yield

ORD record

ord-b1fb0da24afb420a95d8df88c932a7fe

Source dataset

uspto-grants-2010_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07671082B2