Water → HCID 66902461, compound

Temperature

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

ORD record

ord-49d7c6fc6bae4842b00311a0c76211f0

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08153683B2