Dimethyl Sulfoxide → Ethyl 3-methyl-3-(4-oxopiperidin-1-YL)pyrrolidine-1-carboxylate

Temperature

-78 °C

2M Oxalyl chloride solution in dichloromethane (617 mg, 4.86 mmol) was taken into a oven dried round bottom flak and cooled to −78° C. under nitrogen atmosphere. Then dimethyl sulfoxide (767 mg, 9.72 mmol) in anhydrous dichloromethane (5 mL) was added dropwise. After 10 minutes, a solution of ethyl 3-(4-hydroxy-1-piperidyl)-3-methyl-pyrrolidine-1-carboxylate (830 mg, 3.24 mmol) in dichloromethane (10 mL) was cannulated into the flask and stirred at −78° C. for another 10 minutes. Triethylamine (1.31 g, 12.96 mmol) was then added and stirred at −78° C. for 30 minutes, allowed to warm to 0° C. over 30 minutes and was quenched with saturated solution of ammonium chloride (10 mL). The product was extracted into dichloromethane (2×50 mL) and the combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo to afford the title compound as a yellow oil (810 mg, 90%). 1H NMR (CDCl3, 400 MHz): δ 4.18 (m, 2H), 3.88 (m, 1H), 3.62-3.35 (m, 3H), 2.92 (m, 1H), 2.85 (brs, 2H), 2.75 (brs, 1H), 2.48-2.39 (m, 4H), 2.05-1.89 (m, 1H), 1.41 (m, 1H), 1.26 (t, 3H), 1.08 (s, 3H) MS (M+1): 255.12.

1. customdried round bottom flak
2. stirringstirred at −78° C. for 30 minutes
3. temperatureto warm to 0° C. over 30 minutes
4. customwas quenched with saturated solution of ammonium chloride (10 mL)
5. extractionThe product was extracted into dichloromethane (2×50 mL)
6. washthe combined organic layers were washed with brine
7. dry with materialdried over anhydrous Na2SO4
8. concentrationconcentrated in vacuo

ORD record

ord-4d16fc0a49364a36acfa1ea96fe79610

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08119661B2