Isobutane → 1-Trifluoroacetyl-1,4,5,6-tetra-hydropyrazine-2-carboxylic acid tert-butylamide

Temperature

20 °C

50 ml of trifluoroacetic acid was placed in a 500 ml flask under argon. 12.5 g of methanesulfonic acid was added dropwise at 21° C. and 20 g of 2-cyano-1,4,5,6-tetrahydropyrazine methanesulfonic acid salt (97 mmol) was then added in portions, a slight exothermicity being observed. 10 g (178 mmol) of isobutane was then introduced over 1 hour at 20° C. The reaction mixture was stirred for a further 2 hours at 20° C., 13.3 g (111 mmol) of thionyl chloride was then added dropwise at this temperature and stirring was continued for a further 20 hours. 250 ml of dichloromethane was then added, followed by 25 g of sodium acetate in portions. After filtration of the crude solution through Celite®, 30 ml of water was added and the phases were separated. The organic phase was concentrated to dryness. The residual crude product (27.88 g) was chromatographed with ethyl acetate/methanol (4:1) on 300 g of silica gel. The yield (GC) was 29.2 percent. The melting point of the title compound was: 158° to 160° C. (from n-butyl acetate). Other data concerning the title compound was:

1. stirringstirring
2. waitwas continued for a further 20 hours
3. filtrationAfter filtration of the crude solution through Celite®, 30 ml of water
4. additionwas added
5. customthe phases were separated
6. concentrationThe organic phase was concentrated to dryness
7. customThe residual crude product (27.88 g) was chromatographed with ethyl acetate/methanol (4:1) on 300 g of silica gel
8. customThe yield (GC)

ORD record

ord-b22c070aff324743b5f29d95e839b80d

Source dataset

uspto-grants-1999_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05886181