Carbon Dioxide → 4-(3-Fluoropyrazin-2-YL)tetrahydro-2H-pyran-4-OL

Temperature

0 °C

A 2.5M solution of nbuli (4.49 mL, 11.22 mmol)/hexane in THF (3 mL) was first cooled to −78° C. To the cooled solution was added dropwise, 2,2,6,6-tetramethylpiperidine (2.065 mL, 12.24 mmol). The dry ice bath was then switched to a 0° C. bath. The reaction mixture was stirred for 10 min at 0° C. and then the dry ice bath was switched back to recool the reaction mixture to −78° C. To the cooled solution was added 2-fluoropyrazine (1 g, 10.20 mmol), dropwise. After 5 min of stirring at −78° C., a solution of dihydro-2H-pyran-4(3H)-one (0.937 mL, 10.20 mmol) in 0.6 mL of THF was added dropwise. The resulting mixture was allowed to gradually warm to room temperature overnight. Reaction was quenched with saturated NH4Cl and extracted with EtOAc. Purification by Biotage (0-100% EtOAc/hexane) produced product.

1. additionTo the cooled solution was added dropwise
2. customwas then switched to a 0° C.
3. customto −78° C
4. stirringAfter 5 min of stirring at −78° C.
5. temperatureto gradually warm to room temperature overnight
6. customReaction
7. customwas quenched with saturated NH4Cl
8. extractionextracted with EtOAc
9. customPurification by Biotage (0-100% EtOAc/hexane)
10. customproduced product

ORD record

ord-3ec06a9a341c44d68fb3299d42da3fd4

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08329700B2