Reaction #79501

Reaction equation

sodium hydrogencarbonate

1-(1H-imidazol-4-yl)-2-methyl-1-propanone

2-bromo-6-methoxynaphthalene

magnesium

→

1-(1H-imidazol-4-yl)-1-(6-methoxynaphthalen-2-yl)-2-methylpropanol

Yield 84.0%

Solvents

water

THF

THF

THF

Conditions

Workup

1. 1
   Otherhigher than 50° C.
2. 2
   workup.STIRRINGthe mixture was stirred at 15 to 25° C. for 1.5 h
3. 3
   workup.STIRRINGthe mixture was stirred at 15 to 25° C. for 8 h
4. 4
   workup.STIRRINGAfter stirring
5. 5
   OtherAfter partitioning
6. 6
   Extractionthe aqueous layer was extracted with ethyl acetate (5 ml)
7. 7
   Washthe mixture was washed with saturated brine
8. 8
   Concentrationconcentrated under reduced pressure
9. 9
   Filtrationthe crystals were collected by filtration
10. 10
    Washwashed with isopropyl ether (12 ml)
11. 11
    OtherThe crystals were dried in vacuo (40° C.)

Procedure

THF (14 ml) was added to magnesium (0.55 g, 22.4 mmol) under a nitrogen atmosphere. Iodine (3 mg) was added and the mixture was stirred. While keeping the mixture at not higher than 50° C., a solution of 2-bromo-6-methoxynaphthalene (5.15 g, 21.7 mmol.) in THF (12 ml) was added dropwise, and the mixture was stirred at 15 to 25° C. for 1.5 h. A solution of 1-(1H-imidazol-4-yl)-2-methyl-1-propanone (1 g, 7.24 mmol) in THF (5 ml) was added dropwise at −20° C., and the mixture was stirred at 15 to 25° C. for 8 h. A saturated aqueous sodium hydrogencarbonate (5 ml) and water (5 ml) were successively added dropwise. After stirring, the mixture was passed through celite. After partitioning, the aqueous layer was extracted with ethyl acetate (5 ml). The organic layer was combined, and the mixture was washed with saturated brine and concentrated under reduced pressure. The concentration residue was broken up with ethyl acetate (6 ml) and isopropyl ether (12 ml), and the crystals were collected by filtration and washed with isopropyl ether (12 ml). The crystals were dried in vacuo (40° C.) to give 1-(1H-imidazol-4-yl)-1-(6-methoxynaphthalen-2-yl)-2-methylpropanol (1.8 g, yield 84%).

Source