Hexane → HCID 59852752, compound

Temperature

-40 °C

(3-Benzyloxy-2-fluorophenyl) (3-chloropyrazin-2-yl) carbinol: In a 100 mL three-necked round-bottom flask equipped with a N2-inlet and a thermometer was placed THF (28 mL). This was cooled to −40° C. and there was added 2.5 M solution of n-BuLi in hexane (11.52 mL, 28.8 mmole) followed by 2,2,6,6-tetramethylpiperidine (4.84 mL, 28.8 mmole). The temperature of the mixture was allowed to rise to 0° C. and stirring was continued at −5 to 0° C. for 30 minutes. The mixture was then cooled to −70° C., and the chloropyrazine (1.28 mL, 14.4 mmole) was added slowly over 15 minutes and the stirring was continued for 30 minutes. A solution of 3-benzyloxy-2-fluorobenzaldehyde (3.04 g. 13.2 mmole) in THF (7 mL) was then added at −70° C. and stirring was continued at −70 to −60° C. for 2 h. There after the temperature was allowed to rise to room temperature over 1 h. The reaction mixture was quenched with 2 N HCl (6 mL) and stirred overnight at room temperature. The mixture was then evaporated on a rotary evaporator to remove most of the THF. Ethyl acetate (20 mL) was added to the residue. The organic layer was separated, washed with water (10 mL), finally with brine (10 mL), dried over Na2SO4, filtered and concentrated. The crude residue obtained was 4.4 g. The above reaction was repeated four times and the products were combined. This was purified by silica-gel column chromatography using as the eluent ethyl acetate:hexane (30:70) and the title compound (3.8 g, 21%) was obtained.

1. customto rise to 0° C.
2. temperatureThe mixture was then cooled to −70° C.
3. waitthe stirring was continued for 30 minutes
4. stirringstirring
5. waitwas continued at −70 to −60° C. for 2 h
6. waitto rise to room temperature over 1 h
7. customThe reaction mixture was quenched with 2 N HCl (6 mL)
8. stirringstirred overnight at room temperature
9. customThe mixture was then evaporated on a rotary evaporator
10. customto remove most of the THF
11. additionEthyl acetate (20 mL) was added to the residue
12. customThe organic layer was separated
13. washwashed with water (10 mL), finally with brine (10 mL)
14. dry with materialdried over Na2SO4
15. filtrationfiltered
16. concentrationconcentrated
17. customThe crude residue obtained
18. customThe above reaction
19. customThis was purified by silica-gel column chromatography

ORD record

ord-bd666c95d1e84a26becaa6a3fd80fbe6

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07459554B2