Dimethylamine → tert-butyl (2S,4S)-2-(dimethylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate

9.95 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride was added under ice cooling to a 100 mL tetrahydrofuran solution of 10.0 g of (4S)-1-(tert-butoxycarbonyl)-4-hydroxy-L-proline and 8.77 g of 1-hydroxybenzotriazole monohydrate, and the reaction mixture was stirred for 30 minutes at the same temperature. 15.6 g of a 50% dimethylamine aqueous solution was than added to the reaction solution, after which the reaction mixture was stirred for 1 hour at room temperature. 100 mL of chloroform and 50 mL of a 5% potassium carbonate aqueous solution were added to the reaction solution, liquid separation was performed, the aqueous layer was extracted with chloroform (30 mL×2), and the combined organic layer was washed with 30 mL of saturated brine and dried with magnesium sulfate, after which the drying agent was filtered off and the solvent was distilled off under reduced pressure. The residue thus obtained was subjected to column chromatography (silica gel 60, mobile phase: ethyl acetate/n-hexane=1/1 to 10/0; v/v) to obtain 8.66 g of the titled compound (colorless solid).

1. additionthan added to the reaction solution
2. stirringafter which the reaction mixture was stirred for 1 hour at room temperature
3. extractionthe aqueous layer was extracted with chloroform (30 mL×2)
4. washthe combined organic layer was washed with 30 mL of saturated brine
5. dry with materialdried with magnesium sulfate
6. filtrationafter which the drying agent was filtered off
7. distillationthe solvent was distilled off under reduced pressure
8. customThe residue thus obtained

ORDレコード

ord-fa0451fe978d46ea9a63b39814c5ade1

出典データセット

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07528124B2