1,4-Dioxane → ethyl [(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetate

In a round bottom flask, a solution of 1,1-dimethylethyl (3S)-3-[2-(ethyloxy)-2-oxoethyl]-1-pyrrolidinecarboxylate (64.1 g, 249 mmol) in 4M HCl in dioxane (600 mL, 2400 mmol) was stirred at room temperature for 1 h. Analysis of an aliquot by LCMS confirmed complete removal of the BOC group from the starting material. The reaction was concentrated in vacuo to give a pale orange liquid. A solution of this intermediate as the HCl salt in dichloromethane (500 mL) was treated with N,N-diisopropylethylamine (87 mL, 498 mmol) and stirred for 5 min at room temperature. The yellow solution was cooled to 0° C. and was treated with cyclopropanecarbonyl chloride (24.9 mL, 274 mmol) by syringe. The resultant orange solution was allowed to warm to room temperature and stirred for 1 h. The reaction was diluted with water (400 mL), the layers were separated, and the aqueous layer was extracted with 200 mL dichloromethane. The organic layers were combined, dried over MgSO4, concentrated in vacuo, and pumped under high vacuum to give the title compound as an orange liquid (249 mmol, quantitative). MS(ES)+ m/e 226.2 [M+H]+, 451.1 [2M+H]+.

1. customremoval of the BOC group from the starting material
2. concentrationThe reaction was concentrated in vacuo
3. customto give a pale orange liquid
4. temperatureThe yellow solution was cooled to 0° C.
5. temperatureto warm to room temperature
6. stirringstirred for 1 h
7. customthe layers were separated
8. extractionthe aqueous layer was extracted with 200 mL dichloromethane
9. dry with materialdried over MgSO4
10. concentrationconcentrated in vacuo

ORD record

ord-beea3965ed034c97951e6d9ca9ad7401

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802864B2