Diethyl (cyanomethyl)phosphonate → HCID 71143653, compound

To a cooled (at −6 to 0° C.) solution of 1.0 M potassium tert-butoxide in tetrahydrofuran (7.10 mL, 7.10 mmol) was added dropwise a solution of diethyl cyanomethylphosphonate (1.20 mL, 7.43 mmol, Aldrich: Cat. #D91705) in tetrahydrofuran (10.0 mL) over a period of 10 minutes and at −6 to 0° C. The reaction was warmed and stirred at room temperature for 1 hour. The reaction mixture was re-cooled at −6° C. To the reaction mixture was then added a solution of N-isopropyl-4-(3-oxoazetidin-1-yl)benzamide (1.30 g, 5.60 mmol) in tetrahydrofuran (10.0 mL) over a period of 10 minutes. During this time the temperature of the reaction mixture was between −5 to 0° C. The reaction was allowed to warm to room temperature and was stirred for 3 hours. The reaction mixture was filtered through a pad of silica gel and washed with ethyl acetate. The filtrate was concentrated, and the residue was treated with ether. The precipitates formed were collected by filtration to give 0.60 g desired product. The mother liquid was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexane (gradient: 30-80%) to afford the desired product (0.21 g). the total product is 0.81 g (57%). LCMS (M+H)+: m/z=256.1.

1. customat −6 to 0° C
2. temperatureThe reaction was warmed
3. temperatureThe reaction mixture was re-cooled at −6° C
4. customwas between −5 to 0° C
5. temperatureto warm to room temperature
6. stirringwas stirred for 3 hours
7. filtrationThe reaction mixture was filtered through a pad of silica gel
8. washwashed with ethyl acetate
9. concentrationThe filtrate was concentrated
10. additionthe residue was treated with ether
11. customThe precipitates formed
12. filtrationwere collected by filtration

ORD record

ord-84b39297fc634e5fa62f6d47e446a5c3

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691807B2