Hydrochloric Acid → 1-nitrosoazepane-2-carboxylic acid

At 0° C., a solution of 7.80 g (43.4 mmol) of azepan-2-carboxylic acid and 4.10 g (59.5 mmol) of sodium nitrite in 50 ml of water is acidified to pH 3 using HCl (conc.) and then stirred for 1 h. 50 ml of ethyl acetate are added to the reaction mixture, the organic phase is separated off and the aqueous phase is extracted with 2×50 ml of ethyl acetate. The combined organic phases are dried over MgSO4 and freed from the solvent under reduced pressure. The 1-nitrosoazepan-2-carboxylic acid obtained (6.80 g, 67%) is taken up in 15 ml of acetonitrile without further purification, and 12.4 g (59.2 mmol) of trifluoroacetic anhydride are added dropwise at 0° C. After 2 h of stirring at room temperature, 8.19 g (59.2 mmol) of potassium carbonate are added, and stirring is continued for a further 20 min. 40 ml of ethyl acetate and 20 ml of water are added to the reaction mixture, and the aqueous phase is extracted with 3×40 ml of ethyl acetate. The combined organic phases are dried over MgSO4 and freed from the solvent under reduced pressure. Purification by column chromatography on silica gel (cyclohexane/ethyl acetate) gives 5.50 g (90%) of the desired product; log P(HCOOH): 0.6; 1H-NMR (DMSO-d6): 4.45 (m, 2H), 2.56 (m, 2H), 1.83 (m, 4H), 1.57 (m, 2H)

1. customAt 0° C.
2. customthe organic phase is separated off
3. extractionthe aqueous phase is extracted with 2×50 ml of ethyl acetate
4. dry with materialThe combined organic phases are dried over MgSO4

ORD record

ord-f45f8b8dba2b4187bad02bee0b05a12c

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507472B2