Dimethyl Sulfoxide → 878167-05-6

Temperature

-78 °C

To a 100 mL round bottom flask was added DCM (30 mL) and oxalyl chloride (0.88 mL; 10.13 mmol). The solution was cooled to −78° C. and treated with DMSO (1.19 mL; 16.88 mmol). The solution was stirred at −78° C. for 20 minutes and then treated with ethyl 4-(hydroxymethyl)-4-methylpiperidine-1-carboxylate (E5) (1.7 g; 8.44 mmol, dissolved in 10 mL of DCM). The solution was stirred for 30 min at −78° C. and then treated with Et3N (3.53 mL; 25.32 mmol). The solution was stirred at −78° C. for 20 min and then slowly warmed to room temperature and stirred at room temperature for an additional 2 hrs. The solution was then treated with saturated aqueous NaHCO3 (50 mL), diluted with DCM (50 mL), and the layers were separated. The organic layer was washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the product (E6) as an oil, which was used without further purification. LC/MS m/z (M+1) 200.0, retention time 2.23 minutes; (10-99% CH3CN—H2O gradient with 0.03% TFA, 5 min). 1H NMR (400 MHz, CDCl3) δ 9.40 (s, 1H), 4.06 (q, J=7.1 Hz, 2H), 3.66 (dt, J=13.6, 4.7 Hz, 2H), 3.09 (dd, J=10.1, 3.5 Hz, 1H), 3.06 (dd, J=10.2, 3.4 Hz, 1H), 1.86 (dt, J=13.6, 4.4 Hz, 2H), 1.42-1.30 (m, 2H), 1.19 (t, J=7.1 Hz, 3H), 1.02 (s, 3H).

1. stirringThe solution was stirred for 30 min at −78° C.
2. stirringThe solution was stirred at −78° C. for 20 min
3. temperatureslowly warmed to room temperature
4. stirringstirred at room temperature for an additional 2 hrs
5. customthe layers were separated
6. washThe organic layer was washed with brine (50 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure

ORD record

ord-039591fb30d145739089973849306af1

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08263605B2