Hydrochloric Acid → HCID 178449898, compound

Temperature

75 °C

To a solution of 1-amino-1H-pyrrole-2-carboxylic acid ethyl ester (10.8 g, 70.1 mmol) in 250 mL of dioxane in a sealed tube at room temperature was added butyronitrile (61 mL, 700 mmol) followed by 4 N HCl in dioxane (70 mL, 280 mmol). The tube was flushed with Ar, sealed, and heated at 75° C. for 14 h. After cooling to room temperature, the reaction mixture was concentrated in vacuo and then diluted with 240 mL of dioxane. Triethylamine (78 mL, 560 mmol) was added and the reaction was heated at 75° C. for 6 h. After cooling to room temperature, the reaction was concentrated in vacuo to give the crude product. Purification of the crude product by flash column chromatography (SiO2, EtOAc/Hexane 1:1) gave the title compound as a light brown solid (11.6 g, 74%): 1H NMR (CDCl3) δ 6.80 (q, 1H, J=1.96 Hz), 6.59 (t, 1H, J=2.16 Hz), 6.03 (q, 1H, J=2.6 Hz), 4.54 (brs, 2H), 4.11 (q, 2H, J=7.12 Hz), 2.27 (t, 2H, J=7.96 Hz), 1.66 (hex, 2H, J=7.72 Hz), 1.19 (t, 3H, J=7.12 Hz), 0.95 (t, 3H, J=7.32 Hz); 13C NMR (CDCl3) δ 166.7, 160.2, 124.8, 119.8, 116.0, 107.2, 60.0, 35.6, 20.6, 14.9, 14.1; MS (ESI+) 224.10 (M++H).

1. customThe tube was flushed with Ar
2. customsealed
3. temperatureAfter cooling to room temperature
4. concentrationthe reaction mixture was concentrated in vacuo
5. additiondiluted with 240 mL of dioxane
6. temperaturethe reaction was heated at 75° C. for 6 h
7. temperatureAfter cooling to room temperature
8. concentrationthe reaction was concentrated in vacuo
9. customto give the crude product
10. customPurification of the crude product by flash column chromatography (SiO2, EtOAc/Hexane 1:1)

ORD record

ord-47bb87b698fc45a8b0bba3d34c8ebd0a

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07030118B2