1-Methylimidazole → HCID 22714354, compound

Temperature

-70 °C

Butyllithium in hexanes (10 ml) was added slowly at −70° C. under N2 flow to a solution of 1-methylimidazole (1.31 g) in THF (30 ml). The mixture was stirred at −70° C. for 45 minutes. Chlorotriethylsilane (2.7 ml) was added. The mixture was allowed to warm to 15° C. and cooled to −70° C. Butyllithium (10 ml) was added slowly. The mixture was stirred at −70° C. for 1 hour, allowed to warm to −15° C. and cooled to −70° C. A solution of intermediate (6-b) (4.9 g) in THF (60 ml) was added. The mixture was stirred at −70° C. for 30 minutes, then hydrolyzed with water, extracted with ethyl acetate and decanted. The organic layer was dried, filtered and the solvent was evaporated. The residue (8.2 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 96/4/0.2) and crystallized from 2-propanone/diethyl ether. The precipitate was filtered off and dried, yielding 1.5 g (25%) of (±)-3-(3-chlorophenyl)-α-(4-chlorophenyl)-α-(1-methyl-1H-imidazol-5-yl)-2,1-benzisoxazole-5-methanol (interm. 6-c).

1. temperatureto warm to 15° C.
2. temperaturecooled to −70° C
3. stirringThe mixture was stirred at −70° C. for 1 hour
4. temperatureto warm to −15° C.
5. temperaturecooled to −70° C
6. stirringThe mixture was stirred at −70° C. for 30 minutes
7. extractionhydrolyzed with water, extracted with ethyl acetate
8. customdecanted
9. customThe organic layer was dried
10. filtrationfiltered
11. customthe solvent was evaporated
12. customThe residue (8.2 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 96/4/0.2)
13. customcrystallized from 2-propanone/diethyl ether
14. filtrationThe precipitate was filtered off
15. customdried

ORD record

ord-b085b5043a414857b286a24d8796d995

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07253183B2