Boron trifluoride etherate → (R)-3-(5-oxo-4,5-dihydro-[1,2,4]thiadiazol-3-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

(R)-3-(N-Hydroxycarbamimidoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.54 g, 2.36 mmol) and di-imidazol-1-yl-methanethione (0.70 g, 3.53 mmol) were dissolved in THF (15 mL) and stirred for 30 min. The reaction was diluted with water (50 mL) and extracted with EtOAc (50 mL×3). The combined organic layers were dried by MgSO4 and concentrated in vacuo. The residue was dissolved in THF (20 mL) and BF3.Et2O (0.89 ml, 7.06 mmol) was added dropwise. After 1 h of stirring, the reaction was diluted with water (50 mL) and extracted with EtOAc (50 mL×3). The combined organic layers were dried with MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel (20-50% EtOAc/Hexane) to give (R)-3-(5-oxo-4,5-dihydro-[1,2,4]thiadiazol-3-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.42 g, 1.55 mmol, 66%) as a white solid.

1. extractionextracted with EtOAc (50 mL×3)
2. dry with materialThe combined organic layers were dried by MgSO4
3. concentrationconcentrated in vacuo
4. dissolutionThe residue was dissolved in THF (20 mL)
5. stirringAfter 1 h of stirring
6. extractionextracted with EtOAc (50 mL×3)
7. dry with materialThe combined organic layers were dried with MgSO4
8. concentrationconcentrated in vacuo
9. customThe crude material was purified by flash chromatography on silica gel (20-50% EtOAc/Hexane)

ORD record

ord-9edb3cf8c4c448a08203e443bdb39e4c

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08552205B2