Hydrochloric Acid → 5-(Pent-3-yn-2-yloxy)pyrazine-2-carboxylic acid

Temperature

75 °C

50 ml RBF was charged with 3-pentyn-2-ol (2.063 ml, 22.08 mmol) in DMF (10 ml) and potassium t-butoxide (1.24 g, 11.04 mmol) was added portionwise while stirring (cooling in water bath). The mixture was stirred at room temperature for 10 min until all t-BuOK went into solution, then 5-chloropyrazine-2-carboxylic acid (500 mg, 3.15 mmol) was added in portions and the resulting brown suspension was heated at 75° C. for 45 min. The mixture was cooled to room temperature and diluted with water (˜20 ml) until all solids dissolved, then acidified with 2M HCl solution (˜5.5 ml) to pH 2. The resulting solution was extracted with EtOAc, organic layer was washed with water twice then with brine, filtered through pad of celite and concentrated in vacuo. The resulting suspension was diluted with 3 ml heptane/EtOAc (20:1) mixture then filtered. The solid was washed with heptane and dried in vacuo to afford 5-(pent-3-yn-2-yloxy)pyrazine-2-carboxylic acid (424 mg, 2.056 mmol, 65.2% yield) as tan solid. LC/MS (ESI+) m/z=207 (M+H).

1. additionwas added portionwise
2. temperatureThe mixture was cooled to room temperature
3. dissolutiondissolved
4. extractionThe resulting solution was extracted with EtOAc, organic layer
5. washwas washed with water twice
6. filtrationwith brine, filtered through pad of celite
7. concentrationconcentrated in vacuo
8. additionThe resulting suspension was diluted with 3 ml heptane/EtOAc (20:1) mixture
9. filtrationthen filtered
10. washThe solid was washed with heptane
11. customdried in vacuo

ORD record

ord-d4f1233f0ba746bba9187b1f787f0811

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309263B2