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 minutes 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 h. 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 1.6 g of the product (E6) as an oil which was used without further purification. LC/MS m/z (M+1) 200.0, tR 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 minutes 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 h
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-e74e7c2464a445bab4fd33d1cc34025c

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07858635B2