Reaction #1771989

Reaction equation

triethylsilane

lithium triethylborohydride

tetrahydrofuran

triethylsilane

boron trifluoride

boron trifluoride

tert-butyl N-tert-butoxycarbonyl-4,4-dimethylpyroglutamate

tetrahydrofuran

→

Boc-Pro(4,4-dimethyl)-OtBu

tert-butyl N-tert-butoxycarbonyl-4,4-dimethylproline

Conditions

Workup

1. 1
   Otherthe cooling bath was removed
2. 2
   workup.ADDITIONsaturated aqueous sodium bicarbonate (5 mL) was added
3. 3
   OtherThe reaction mixture was immersed in an ice/water bath
4. 4
   workup.ADDITION30% aqueous hydrogen peroxide (10 drops) was added
5. 5
   Concentrationthe reaction mixture was concentrated in vacuo
6. 6
   Otherto remove the tetrahydrofuran
7. 7
   workup.ADDITIONThe aqueous solution was diluted with water (10 mL)
8. 8
   Extractionextracted with dichloromethane (3×40 mL)
9. 9
   DryingThe organic layers were dried (Na2SO4)
10. 10
    Filtrationfiltered
11. 11
    Concentrationconcentrated
12. 12
    workup.DISSOLUTIONThe residue was dissolved in dichloromethane (20 mL)
13. 13
    workup.STIRRINGStirring
14. 14
    workup.ADDITIONwere added
15. 15
    workup.STIRRINGAfter stirring at −78° C. for an additional two hours
16. 16
    Otherthe cooling bath was removed
17. 17
    workup.ADDITIONsaturated aqueous sodium bicarbonate (4 mL) was added
18. 18
    ExtractionAfter 5 minutes the mixture was extracted with dichloromethane (3×40 mL)
19. 19
    DryingThe organic layers were dried (Na2SO4)
20. 20
    Filtrationfiltered
21. 21
    Concentrationconcentrated

Procedure

To a solution of tert-butyl N-tert-butoxycarbonyl-4,4-dimethylpyroglutamate (2.0 mmol) in tetrahydrofuran (5 mL) stirring at −78° C., was added a 1M solution of lithium triethylborohydride in tetrahydrofuran (2.4 mL, 2.4 mmol) dropwise over 5 minutes. After 30 minutes, the cooling bath was removed and saturated aqueous sodium bicarbonate (5 mL) was added. The reaction mixture was immersed in an ice/water bath and 30% aqueous hydrogen peroxide (10 drops) was added. The solution was stirred for 20 minutes at 0° C., then the reaction mixture was concentrated in vacuo to remove the tetrahydrofuran. The aqueous solution was diluted with water (10 mL) and extracted with dichloromethane (3×40 mL). The organic layers were dried (Na2SO4), filtered and concentrated. The residue was dissolved in dichloromethane (20 mL) and triethylsilane (310 μL, 2.0 mmol), then cooled to −78° C. and boron trifluoride diethyletherate (270 μL, 2.13 mmol) was added dropwise. Stirring was continued for 30 minutes, at which time additional triethylsilane (310 μL, 2.0 mmol) and boron trifluoride diethyletherate (270 μL, 2.13 mmol) were added. After stirring at −78° C. for an additional two hours, the cooling bath was removed and saturated aqueous sodium bicarbonate (4 mL) was added. After 5 minutes the mixture was extracted with dichloromethane (3×40 mL). The organic layers were dried (Na2SO4), filtered and concentrated to give Boc-Pro(4,4-dimethyl)-OtBu.

Source