Reaction #499714

Reaction equation

ammonium chloride

7-chloromethoxy-1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid benzyl ester

1-tert-butoxycarbonylpiperidine-4-carboxylic acid ethyl ester

lithium diisopropylamide tetrahydrofuran

→

title compound

Yield 47.9%

7-(1-tert-Butoxycarbonyl-4-ethoxycarbonylpiperidin-4-ylmethoxy)-1,2,3,4-tetrahydroisoquinoline-2-carboxylic Acid Benzyl Ester

Yield 47.9%

Solvents

water

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   workup.STIRRINGin stirring
2. 2
   workup.ADDITIONwere added with ice-
3. 3
   Temperaturecooling
4. 4
   ExtractionThe mixture was extracted with ethyl acetate
5. 5
   Washthe extract was washed successively with water and saturated brine
6. 6
   DryingThe organic layer was dried over anhydrous sodium sulfate
7. 7
   Otherthe solvent was evaporated
8. 8
   Otherthe obtained residue was purified by silica gel column chromatography (hexane:acetone=7:1)
9. 9
   Otherdried under reduced pressure

Procedure

To a solution of 1-tert-butoxycarbonylpiperidine-4-carboxylic acid ethyl ester (300 mg) in tetrahydrofuran (3 ml) was dropwise added a 1.5M lithium diisopropylamide-tetrahydrofuran solution (0.97 ml) at −70° C., and the mixture was stirred at the same temperature for 50 min. Then, a solution of 7-chloromethoxy-1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid benzyl ester (213 mg) in tetrahydrofuran (3 ml) was dropwise added at the same temperature, and the mixture was allowed to warm to room temperature in 2 hours in stirring. After completion of the reaction, aqueous ammonium chloride solution and water were added with ice-cooling. The mixture was extracted with ethyl acetate and the extract was washed successively with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated and the obtained residue was purified by silica gel column chromatography (hexane:acetone=7:1) and dried under reduced pressure to give the title compound (170 mg).

Source