(1R,5S)-tert-butyl 3-(trifluoromethylsulfonyloxy)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate

(1R,5S)-tert-butyl 3-(trifluoromethylsulfonyloxy)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate Property

Boiling point:

392.9±42.0 °C(Predicted)

Density 

1.42±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

pka

-3.68±0.40(Predicted)

form 

Crystalline Powder or LMS

color 

White to off-white

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H332Harmful if inhaled

H335May cause respiratory irritation

Precautionary statements

P280Wear protective gloves/protective clothing/eye protection/face protection.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P310Immediately call a POISON CENTER or doctor/physician.

(1R,5S)-tert-butyl 3-(trifluoromethylsulfonyloxy)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate Chemical Properties,Usage,Production

Synthesis

To a solution of tert-butyl 3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate (1.0 g, 4.2 mmol) in tetrahydrofuran (21.1 mL) was added slowly and dropwise lithium hexamethyldisilanilaminate (LHMDS, 4.64 mL, 4.64 mmol) under nitrogen atmosphere. The temperature of the reaction system was maintained at -50 °C, followed by a slow warming to -30 °C and continuous stirring for 1 hour. A solution of N-phenylbis(trifluoromethanesulfonyl)imide (1.66 g, 4.64 mmol) in tetrahydrofuran (1.0 mL) was added dropwise to the reaction mixture at -30 °C. After the dropwise addition was completed, the reaction mixture was gradually warmed to 25 °C and stirring was continued for 4 hours. Upon completion of the reaction, the reaction was quenched by the addition of aqueous ammonium chloride solution (10 mL), followed by extraction of the aqueous layer with dichloromethane (3 x 10 mL). The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: 0-30% ethyl acetate/hexane) to afford the target product 8-Boc-3-(trifluoromethylsulfonyloxy)-8-azabicyclo[3.2.1]oct-3-ene (2.2 g, 95% yield). Mass spectrometry (electrospray positive ion mode) analysis result: C13H18F3NO5S theoretical molecular weight 357, measured value 358 [M+H]+.

References

[1] Patent: WO2018/218197, 2018, A2. Location in patent: Paragraph 0372; 0373
[2] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 10, p. 1817 - 1820
[3] Patent: WO2012/27234, 2012, A1. Location in patent: Page/Page column 41
[4] Patent: WO2016/138532, 2016, A1. Location in patent: Paragraph 0343
[5] Patent: US2017/112833, 2017, A1. Location in patent: Paragraph 0518-0519