Chlorotrimethylsilane → HCID 178429767, compound

Temperature

-20 °C

A dry 100 mL round-bottomed flask equipped with a magnetic stir bar under an atmosphere of N2 was charged with 528 mg (2.35 mmol) of 2-(bicyclo[2.2.1]heptan-2-ylamino)-5-methylthiazol-4(5H)-one in 5 mL of anhydrous THF. The reaction was cooled to −20° C. and 5.0 mL (5.0 mmol) of NaHMDS (11.0M in THF) were added drop-wise via syringe. The resulting reaction mixture was stirred at −20° C. for 30 min then 0.86 mL (6.78 mmol) of TMSCl was added drop-wise via syringe. The reaction mixture was held at −20° C. for 15 min, and then the mixture was allowed to warm to ambient temperature. After stirring the reaction mixture for an additional 1 h, the mixture was concentrated in vacuo. The reaction flask was again equipped with a magnetic stir bar and placed under an N2 atmosphere. Anhydrous CH3CN was added, and 978 mg (2.58 mmol) of S-(trifluoromethyl)dibenzothiophenium-3-sulfonate C2 H5OH was added to the reaction mixture in one portion, and the resulting suspension was stirred at ambient temperature for 19 h. The solids were then removed by filtration through a Celite pad, and the reaction flask and pad were rinsed with CH2Cl2. The organic layer was washed with 20 mL of 1:1 H2O/sat'd NH4Cl, and the aqueous layer was extracted with an additional portion of CH2Cl2. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. Flash chromatography (SiO2, CH2Cl2 to 5% MeOH/CH2Cl2) provided the desired compound. MS (ESI, pos. ion) m/z: 293.1 (M+H).

1. customA dry 100 mL round-bottomed flask equipped with a magnetic stir bar under an atmosphere of N2
2. customThe resulting reaction mixture
3. waitThe reaction mixture was held at −20° C. for 15 min
4. temperatureto warm to ambient temperature
5. stirringAfter stirring the reaction mixture for an additional 1 h
6. concentrationthe mixture was concentrated in vacuo
7. customThe reaction flask was again equipped with a magnetic stir bar
8. additionAnhydrous CH3CN was added
9. stirringthe resulting suspension was stirred at ambient temperature for 19 h
10. customThe solids were then removed by filtration through a Celite pad
11. washthe reaction flask and pad were rinsed with CH2Cl2
12. washThe organic layer was washed with 20 mL of 1:1 H2O/sat'd NH4Cl
13. extractionthe aqueous layer was extracted with an additional portion of CH2Cl2
14. washThe combined organic layers were washed with brine
15. dry with materialdried over MgSO4
16. filtrationfiltered
17. concentrationconcentrated in vacuo

ORD record

ord-9adb0540f2d64a4e93a00007c768e2f0

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07253196B2