Reaction #464484

Reaction equation

lithium diisopropylamide mono(tetrahydrofuran)

4,5-diphenyloxazole

2-[(3-methoxyphenyl)methyl]cyclohexanone

ammonium chloride

→

2-[(1RS,2RS)-1-hydroxy-2-[(3-methoxyphenyl)methyl]-cyclohexyl]-4,5-diphenyloxazole

Yield 37.6%

Solvents

cyclohexane

tetrahydrofuran

diethyl ether

tetrahydrofuran

carbon tetrachloride

Conditions

Workup

1. 1
   Otherto rise gradually to room temperature
2. 2
   Otherpartitioned between ethyl acetate and 1N hydrochloric acid
3. 3
   OtherThe ethyl acetate layer was separated
4. 4
   Washwashed successively with 1N hydrochloric acid (twice), sodium bicarbonate aqueous solution, and brine
5. 5
   Dryingdried over magnesium sulfate
6. 6
   Otherevaporated in vacuo
7. 7
   OtherThe oily residue was chromatographed (n-hexane - ethyl acetate (10:1)) over silica gel

Procedure

A 1.5 M solution of lithium diisopropylamide mono(tetrahydrofuran) in cyclohexane (19.9 ml) was added dropwise to a stirred solution of 4,5-diphenyloxazole (6.0 g) in tetrahydrofuran (36 ml) and diethyl ether (18 ml) under dry ice--carbon tetrachloride cooling and the mixture was stirred at the same temperature for a while and at 0° C. for a while. A solution of 2-[(3-methoxyphenyl)methyl]cyclohexanone (5.92 g) in tetrahydrofuran (16 ml) was added to the reaction mixture under dry ice-acetone cooling, and the resulting mixture was stirred at the same temperature for several hours. Then the reaction temperature was allowed to rise gradually to room temperature and the reaction mixture was allowed to stand at room temperature overnight. The mixture was treated with ammonium chloride aqueous solution and partitioned between ethyl acetate and 1N hydrochloric acid. The ethyl acetate layer was separated and washed successively with 1N hydrochloric acid (twice), sodium bicarbonate aqueous solution, and brine, dried over magnesium sulfate, and evaporated in vacuo. The oily residue was chromatographed (n-hexane - ethyl acetate (10:1)) over silica gel. The first eluate afforded 2-[(1RS,2RS)-1-hydroxy-2-[(3-methoxyphenyl)methyl]-cyclohexyl]-4,5-diphenyloxazole (4.48 g) as pale yellow paste.

Source