Dimethyl Sulfoxide → (S)-1-(3-Benzyloxy-propyl)-3-methyl-piperazin-2-one

Dimethyl sulfoxide (7.60 g, 97.2 mmol) was added dropwise at −78° C. to a solution of oxalyl chloride (6.17 g, 48.6 mmol) in dichloromethane (300 ml) then after 10 min a solution of {(S)-1-[(3-benzyloxy-propyl)-(2-hydroxy-ethyl)-carbamoyl]-ethyl}-carbamic acid tert-butyl ester (16.8 g, 44.2 mmol) in dichloromethane (300 ml) was added at a temperature below −70° C. After 1 h, triethylamine (16.1 g, 159 mmol) was added, then after 15 min the ice bath was removed. The reaction mixture was allowed to reach room temperature, then washed with sat. aq. sodium hydrogencarbonate solution and brine, dried (MgSO4), filtered, and evaporated. The residue was taken up in dichloromethane (300 ml), then triethylsilane (10.3 g, 88.4 mmol) and trifluoroacetic acid (75.6 g, 663 mmol) were added at room temperature. The reaction mixture was stirred at room temperature for 16 h, then evaporated. The residue was dissolved in dichloromethane (100 ml), then triethylamine (60 ml) was added at 0° C. over 30 min, then after 45 min the reaction mixture was concentrated. The residue was dissolved in ethyl acetate and water, then 2 M aq. sodium carbonate solution was added under ice cooling. The organic layer was separated, washed with brine, dried (MgSO4), filtered, and evaporated. Chromatography (SiO2; dichloromethane/methanol/25% aq. ammonia solution 90:10:0.25) produced the title compound (9.07 g, 78%). Colorless oil, MS (ISP)=263.4 (M+H)+.

1. customafter 15 min the ice bath was removed
2. customto reach room temperature
3. washwashed with sat. aq. sodium hydrogencarbonate solution and brine
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. customevaporated
7. customevaporated
8. dissolutionThe residue was dissolved in dichloromethane (100 ml)
9. additiontriethylamine (60 ml) was added at 0° C. over 30 min
10. concentrationafter 45 min the reaction mixture was concentrated
11. dissolutionThe residue was dissolved in ethyl acetate
12. additionwater, then 2 M aq. sodium carbonate solution was added under ice cooling
13. customThe organic layer was separated
14. washwashed with brine
15. dry with materialdried (MgSO4)
16. filtrationfiltered
17. customevaporated

ORD record

ord-419c2134fce147a68efaecd97e2696f1

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071586B2