Potassium Carbonate → HCID 11010976, compound

Temperature

100 °C

A mixture of 4-(2-amino-2-methylpropyl)phenol acetic acid salt (22.53 g, 100 mmol), powdered K2CO3 (34.55 g, 250 mmol) and DMAC (275 ml) was heated to 100° C. Toluene (94 ml) was added and the mixture slowly heated to reflux. The reflux temperature was raised by distillation of toluene and water until it reached 140° C. The mixture was then cooled to below 100° C. and 2-chloronicotinonitrile (13.86 g, 100 mmol) added with a toluene rinse (50 ml). The mixture was again heated to reflux and the reflux temperature raised to 140° C. as before. Then the water trap was filled with toluene and the reflux continued for 40 min., at which point HPLC showed no 2-chloronicotinonitrile remained but the reaction was not complete. After cooling the reaction below reflux, additional 2-chloronicotinonitrile (0.63 g, 4.5 mmol) was added and reflux continued for 90 min. The reaction was cooled to room temperature and the solids filtered with a toluene wash. The filtrate was concentrated on a rotary evaporator to 41 g of syrup which was dissolved in EtOAc (200 ml). This solution was washed with water (200 ml) and the aqueous layer back-extracted with EtOAc (50 ml). The combined organic layers were washed with water (3×200 ml) and concentrated in vacuo to 26.93 g of solid, ˜100% of theory. HPLC indicated 94.3% purity. 1H NMR (300 MHz, DMSO-d6) was consistent with the desired product.

1. temperaturethe mixture slowly heated to reflux
2. customreached 140° C
3. temperatureThe mixture was then cooled to below 100° C.
4. washrinse (50 ml)
5. temperatureThe mixture was again heated
6. temperatureto reflux
7. temperaturethe reflux temperature raised to 140° C. as before
8. additionThen the water trap was filled with toluene
9. temperatureAfter cooling
10. customthe reaction
11. temperaturebelow reflux
12. temperaturereflux
13. waitcontinued for 90 min
14. temperatureThe reaction was cooled to room temperature
15. filtrationthe solids filtered with a toluene
16. washwash
17. concentrationThe filtrate was concentrated on a rotary evaporator to 41 g of syrup which
18. dissolutionwas dissolved in EtOAc (200 ml)
19. washThis solution was washed with water (200 ml)
20. extractionthe aqueous layer back-extracted with EtOAc (50 ml)
21. washThe combined organic layers were washed with water (3×200 ml)
22. concentrationconcentrated in vacuo to 26.93 g of solid, ˜100% of theory

ORD record

ord-0ca1dd4ac3e2415792f740483d6decb2

Source dataset

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06686372B2