Reaction #167000

Reaction equation

Pyrrolidine-1,2-dicarboxylic acid 2-[2-(7-bromo-dibenzothiophen-3-yl)-2-oxo-ethyl]ester 1-tert-butyl ester

tributyl(1-ethoxyvinyl)tin

NBS

2-Aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-tert-butyl ester

→

2-Aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 3-(2-{7-[2-(1-tert-butoxycarbonyl-pyrrolidine-2-carbonyloxy)-acetyl]-dibenzothiophen-3-yl}-2-oxo-ethyl)ester 2-tert-butyl ester

Solvents

MeCN

dioxane

DMF

DMF

water

ethyl acetate

EtOAc

Conditions

Workup

1. 1
   TemperatureThe reaction was cooled to room temperature
2. 2
   Washwashed with saturated sodium bicarbonate solution
3. 3
   DryingThe organic layer dried (MgSO4)
4. 4
   Concentrationconcentrated down
5. 5
   Otherdried on vacuum
6. 6
   Otherto give residue which
7. 7
   workup.STIRRINGThe reaction was stirred at room temperature overnight
8. 8
   OtherThe reaction crude
9. 9
   Washwashed with saturated sodium bicarbonate solution
10. 10
    DryingThe organic layer dried (MgSO4)
11. 11
    Concentrationconcentrated
12. 12
    Otherpurified by flash column chromatography (silica gel, 0 to 50% ethyl acetate/hexane)

Procedure

[1,1′-Bis(triphenylphosphine)dichloropalladium(II) (3%, 14 mg, 0.02 mmol) and tetrakis(triphenylphosphine)palladium (3%, 23 mg, 0.02 mmol) were added to the mixture of Pyrrolidine-1,2-dicarboxylic acid 2-[2-(7-bromo-dibenzothiophen-3-yl)-2-oxo-ethyl]ester 1-tert-butyl ester (345 mg, 0.665 mmol) and tributyl(1-ethoxyvinyl)tin (1.2 eq., 0.269 mL) in 5 mL dioxane. The reaction was heated to 80° C. under Are for 4 hours. The reaction was cooled to room temperature. 1.5 mL water was added and followed by NBS (1 eq., 142 mg). The reaction was stirred at room for 1 hour. The reaction mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate solution. The organic layer dried (MgSO4), concentrated down and dried on vacuum to give residue which was used in next step. The residue was dissolved in 4 mL anhydrous DMF. 2-Aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-tert-butyl ester (2 eq., 321 mg, 1.33 mmol g) was added, followed by TEA (2.2 eq., 204 mg) in 4 mL MeCN and 3 mL DMF dropwise. The reaction was stirred at room temperature overnight. The reaction crude was diluted with EtOAc and washed with saturated sodium bicarbonate solution. The organic layer dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 0 to 50% ethyl acetate/hexane) to give 2-Aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 3-(2-{7-[2-(1-tert-butoxycarbonyl-pyrrolidine-2-carbonyloxy)-acetyl]-dibenzothiophen-3-yl}-2-oxo-ethyl)ester 2-tert-butyl ester as a yellow residue (92.5 mg, yield 19%). LCMS-ESI−: calc'd for C38H44N2O10S: 720.83. Found: 743.2 (M+Na+).

Source