1,4-Dioxane → HCID 86715179, compound

In a round bottom flask, a solution of 1,1-dimethylethyl 3-[2-(ethyloxy)-2-oxoethyl]-1-azetidinecarboxylate (10.55 g, 43.3 mmol) in 4M HCl in dioxane (50 mL, 200 mmol) was stirred at room temperature for 1 h. Analysis by LCMS showed that the reaction was complete; conversion was observed to the des-BOC intermediate [M+H]+=144.0 (by ELS, no UV214 detection) and an unknown [M+H]+=179.9. The reaction was concentrated in vacuo. A solution of this intermediate (as the HCl salt) in dichloromethane (50 mL) was treated with N,N-diisopropylethylamine (15.14 mL, 87 mmol) and stirred for 2 min at room temperature. The pale yellow solution was treated with cyclopropanecarbonyl chloride (4.33 mL, 47.7 mmol) by syringe at room temperature and then stirred for 1 h. The reaction was diluted with water (200 mL), the layers were separated and the aqueous layer was extracted with dichloromethane (100 mL). The organic layers were combined, dried over MgSO4, and concentrated in vacuo to give the title compound as an orange liquid (10.54 g, 65% pure, 75% yield). This product could also be prepared by using 10% TFA in dichloromethane. 1H NMR in DMSO-d6 showed ˜2:1 desired product:by-product. MS(ES)+ m/e 211.9 [M+H]+.

1. concentrationThe reaction was concentrated in vacuo
2. stirringstirred for 1 h
3. customthe layers were separated
4. extractionthe aqueous layer was extracted with dichloromethane (100 mL)
5. dry with materialdried over MgSO4
6. concentrationconcentrated in vacuo

ORD record

ord-68689b3767254709a95fd2ae2c4e06c6

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802864B2