Dimethyl Sulfoxide → HCID 10990126, compound

Temperature

-78 °C

A solution of oxalyl chloride in dichloromethane (2M, 13.67 mL, 27.33 mmol) was cooled to −78° C. under nitrogen atmosphere and was added to a solution of dimethylsulfoxide (3.87 mL, 54.0 mmol) in dichloromethane (40 mL) at −78° C. under nitrogen atmosphere via cannula. After 10 minutes, a solution of tert-butyl 4-(4-hydroxy-1-piperidyl)-4-methyl-piperidine-1-carboxylate (18.0 mmol) in dichloromethane (20 mL) was added at −78° C. under nitrogen atmosphere to the reaction mixture via cannula. The mixture was stirred at −78° C. for 10 minutes and then triethylamine (10.07 mL, 72.0 mmol) was added dropwise. The reaction was stirred at −78° C. under nitrogen atmosphere for another 20 minutes, then allowed to warm up to 0° C. over 1 hour. The reaction was quenched with water (50 mL) and diluted with dichloromethane (100 mL). The phases were separated and the aqueous layer was extracted with dichloromethane (2×50 mL). The combined organic phases were washed with saturated aqueous ammonium chloride, brine, dried over Na2SO4 and concentrated in vacuo to afford the title compound as yellow oil (5.02 g, 94%), which was used for the subsequent step without further purification. MS (M+1): 297.24.

1. stirringThe reaction was stirred at −78° C. under nitrogen atmosphere for another 20 minutes
2. temperatureto warm up to 0° C. over 1 hour
3. customThe reaction was quenched with water (50 mL)
4. additiondiluted with dichloromethane (100 mL)
5. customThe phases were separated
6. extractionthe aqueous layer was extracted with dichloromethane (2×50 mL)
7. washThe combined organic phases were washed with saturated aqueous ammonium chloride, brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated in vacuo

ORD record

ord-5ecc93f5c4d44d7a8d26e016ea25a7d0

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08119661B2