Ammonia → 2,2-Difluoropent-4-enamide

To a stirred solution of 2,2-difluoropent-4-enoic acid (27.2 g, 0.2 mol) in hexane (200 mi) in a three-neck flask equipped with a reflux condenser and M2 inlet is added DMF (20 drops, catalytic) and oxalyl chloride (20 mL, 0.23 mol). The mixture is stirred at room temperature for 2 h, when no further evolution of gas is seen. The solution is cooled in an ice/brine bath, the N2 inlet is replaced by an empty CaCl2 tube (to trap any solid material blown out of the flask), and a stream of NH3 gas is passed into the flask. The gas flow is maintained for 30 min after the initial vigorous reaction has subsided. The mixture is then poured into H2O (1 L) and Et2O (0.5 L). The glassware is washed with H2O and Et2O, and the washings are added to this mixture. Celite is added and insoluble material is removed by filtration. The phases are separated. The Et2O phase is washed once with brine, dried over Na2SO4, and concentrated. The aqueous phase is extracted twice with CH2Cl2. The combined extracts are washed once with brine, dried over Na2SO4, combined with the residue of the ethereal phase, and concentrated. The residue is distilled to give the title amide (20.6 g, 76%) bp 100°-110° C/10 Torr, as a slightly yellow oil which solidifies on cooling, mp 33°-35° C. 1H NMR (CDCl3)δ7.0-6.0 (2H, br.d), 5.75 (1 H, ddt, J=18, 9, 6 Hz), 5.3 (2 H, m), 2.87 (2 H, dt, J=6, 17 Hz). 19F NMR (δC6F6 =O) δ-56.0 (t, J=17 Hz).

1. temperatureThe solution is cooled in an ice/brine bath
2. custom(to trap any solid material blown out of the flask
3. temperatureThe gas flow is maintained for 30 min after the initial
4. customvigorous reaction
5. washThe glassware is washed with H2O and Et2O
6. additionthe washings are added to this mixture
7. additionCelite is added
8. custominsoluble material is removed by filtration
9. customThe phases are separated
10. washThe Et2O phase is washed once with brine
11. dry with materialdried over Na2SO4
12. concentrationconcentrated
13. extractionThe aqueous phase is extracted twice with CH2Cl2
14. washThe combined extracts are washed once with brine
15. dry with materialdried over Na2SO4
16. concentrationconcentrated
17. distillationThe residue is distilled

ORD record

ord-44c646983dec4085b7e7913a164bfdda

Source dataset

uspto-grants-1994_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05286726