Cyclobutylcarbinol → (S~2~S)-N-[(E)-Cyclobutylmethylidene]-2-methylpropane-2-sulfinamide

Into a 20-L 4-necked round-bottom flask was placed a solution of cyclobutylmethanol (1000 g, 11.61 mol) in dichloromethane (10 L). This was followed by the addition of Dess-Martin periodinane (4683 g, 11.04 mol) in several batches at 10-15° C. over 120 min. The resulting solution was stirred for 2 h at room temperature and then quenched by the addition of 20 L of cold, saturated aqueous sodium bicarbonate solution. Solids were removed by filtration and washed with 5 L of dichloromethane. The filtrate was extracted with dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with DCM:PE (2:1). This resulted in 100 L of cyclobutanecarbaldehyde in dichloromethane and petroleum ether solution. Step 2: Into a 50-L barrel was placed cyclobutanecarbaldehyde in dichloromethane and petroleum ether (33 L of the solution described at the end of Step 1), (S)-2-methylpropane-2-sulfinamide (500 g, 4.13 mol) and copper sulfate (2 kg, 13.33 mol). The resulting solution was stirred for 2 days at room temperature. Solids were removed by filtration. The filtrate was concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1:5) to afford (S)—N-[(1E)-cyclobutylmethylidene]-2-methylpropane-2-sulfinamide.

1. customInto a 20-L 4-necked round-bottom flask was placed
2. customquenched by the addition of 20 L of cold, saturated aqueous sodium bicarbonate solution
3. customSolids were removed by filtration
4. washwashed with 5 L of dichloromethane
5. extractionThe filtrate was extracted with dichloromethane
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated under vacuum
8. washeluted with DCM
9. customThis resulted in 100 L of cyclobutanecarbaldehyde in dichloromethane
10. stirringThe resulting solution was stirred for 2 days at room temperature
11. customSolids were removed by filtration
12. concentrationThe filtrate was concentrated under vacuum
13. washeluted with ethyl acetate/petroleum ether (1:5)

ORD-Eintrag

ord-ed493089dfd84ff38cf4e05a67d99407

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08846657B2