Hydrochloric Acid → HCID 77230264, compound

Temperature

0 °C

2,2,6,6-Tetramethylpiperidine (9.58 mL, 56.4 mmol) was dissolved in dry THF (100 mL), and cooled to 0° C., whilst n-butyllithium (1.6M in hexanes, 35.2 mL, 56.43 mmol) was added over 15 min. The resulting solution was cooled to −78° C., and 6-bromonicotinic acid (3.8 g, 18.8 mmol.) was added as a solid in four equal portions, with stirring over 10 min. Stirring was continued at this temperature for 1.5 h, and the resulting deep-red solution was treated with dry DMF (10 mL) and allowed to warm to room temperature overnight. The mixture was poured onto water (200 mL) and acidified with 1M HCl, and the aqueous phase was extracted with EtOAc (×4). The combined organic phases were washed (brine), dried (sodium sulfate) and concentrated to give a yellow oil, which was dissolved in THF (25 mL) and treated with hydrazine (1M in THF, 19 mL). The precipitate was filtered, and dissolved in ethanol (50 mL) and heated to reflux in the presence of potassium acetate (5 g). The mixture was concentrated under reduced pressure and the brown oily solid was triturated with diethyl ether and the ethereal solution was subjected to flash chromatography (50% ethyl acetate/isohexane) to give a white solid (0.5 g, 12%). 1H NMR (400 MHz) DMSO-d6 δ: 8.21 (1H, s), 8.36 (1H, s), 9.20 (1H, s), 13.09, (1H, s). MS (ES M+1) 226/228.

1. temperatureThe resulting solution was cooled to −78° C.
2. stirringStirring
3. waitwas continued at this temperature for 1.5 h
4. temperatureto warm to room temperature overnight
5. additionThe mixture was poured onto water (200 mL)
6. extractionthe aqueous phase was extracted with EtOAc (×4)
7. washThe combined organic phases were washed (brine)
8. dry with materialdried (sodium sulfate)
9. concentrationconcentrated
10. customto give a yellow oil, which
11. filtrationThe precipitate was filtered
12. dissolutiondissolved in ethanol (50 mL)
13. temperatureheated
14. temperatureto reflux in the presence of potassium acetate (5 g)
15. concentrationThe mixture was concentrated under reduced pressure
16. customthe brown oily solid was triturated with diethyl ether

ORD record

ord-9d7edc3bbf9a4161854d8c841e619fed

Source dataset

uspto-grants-2008_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07329659B2