Diisopropylamine → 4,6-Dichloro-1-hydroxyfuro[3,4-c]pyridin-3(1H)-one

Temperature

-78 °C

N-Butyllithium (46.7 ml) was added to 100 ml of THF at −78° C., followed by the addition of diisopropylamine (16.65 ml) over 15 min. The mixture was stirred for 1 h at −78° C., then 2,6-dichloronicotinic acid (7.12 g) was added over 10 min. Stirring at −78° C. was continued for 2 h, then DMF (23.26 ml) was added dropwise maintaining the T<−70° C. The mixture was stirred for 1 h at −78° C., warmed to −50° C. for 30 min, and allowed to warm to RT. The mixture was quenched carefully by the addition of 2 N HCl (167 ml) until acidic pH was reached. The mixture was extracted with EtOAc, the organic layers were washed with brine and dried over MgSO4. After evaporation of the solvents the crude material was used without further purification: brown solid.

1. stirringStirring at −78° C.
2. waitwas continued for 2 h
3. temperaturemaintaining the T<−70° C
4. stirringThe mixture was stirred for 1 h at −78° C.
5. temperaturewarmed to −50° C. for 30 min
6. temperatureto warm to RT
7. customThe mixture was quenched carefully by the addition of 2 N HCl (167 ml) until acidic pH
8. extractionThe mixture was extracted with EtOAc
9. washthe organic layers were washed with brine
10. dry with materialdried over MgSO4
11. customAfter evaporation of the solvents the crude material
12. customwas used without further purification

ORD record

ord-64a76638ddaa4f728e0261e764fb8397

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09315500B2