Potassium Carbonate → tert-butyl(2S,4S)-2-(azetidin-1-ylcarbonyl)-4-hydroxypyrrolidine-1-carboxylate

2.19 g of 1-hydroxybenzotriazole monohydrate and 2.49 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride were added under ice cooling to a 25 mL N,N-dimethylformamide solution of 2.50 g of (4S)-1-(tert-butoxycarbonyl)-4-hydroxy-L-proline and stirred for 30 minutes. 1.23 g of trimethyleneimine was added dropwise over a period of 1 minute to the reaction mixture, and the reaction mixture was stirred for 16 hours at room temperature. 30 mL of ethyl acetate and 20 mL of a 5% potassium carbonate aqueous solution were added to the reaction solution and stirred for 30 minutes. After liquid separation, the aqueous layer was extracted with ethyl acetate (50 mL×2), and the combined organic layer was washed with water (50 mL×3) and 50 mL of saturated brine, and then dried with anhydrous magnesium sulfate, after which the drying agent was filtered off, and the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel 60, mobile phase: ethyl acetate) to obtain 2.81 g of the titled compound (pale yellow solid).

1. stirringthe reaction mixture was stirred for 16 hours at room temperature
2. stirringstirred for 30 minutes
3. customAfter liquid separation
4. extractionthe aqueous layer was extracted with ethyl acetate (50 mL×2)
5. washthe combined organic layer was washed with water (50 mL×3) and 50 mL of saturated brine
6. dry with materialdried with anhydrous magnesium sulfate
7. filtrationafter which the drying agent was filtered off
8. concentrationthe reaction mixture was concentrated under reduced pressure
9. customThe residue was purified by column chromatography (silica gel 60, mobile phase: ethyl acetate)

ORD-Eintrag

ord-5681ef9cb6e84b619de87e97ba9bcd3f

Quelldatensatz

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07528124B2