Reaktion #504621

Reaktionsgleichung

HATU

4-Bromo-benzene-1,2-diamine

Boc-L-proline

4-methylmorpholine

→

2-(6-Bromo-1H-benzoimidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Ausbeute 66.4%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeReaction mixture
2. 2
   Einengenconcentrated
3. 3
   workup.DISSOLUTIONResidue was dissolved in ethyl acetate
4. 4
   Waschenwashed with 5% lithium chloride solution (2×), brine
5. 5
   Trocknendried (MgSO4)
6. 6
   Einengenconcentrated
7. 7
   Sonstigepurified by flash column chromatography (silica gel, 30 to 60% ethyl acetate/hexanes) to a dark brown foam
8. 8
   workup.DISSOLUTIONBrown foam was dissolved in ethanol (100 mL)
9. 9
   SonstigeReaction mixture
10. 10
    Temperaturwas cooled
11. 11
    Einengenconcentrated
12. 12
    workup.DISSOLUTIONResidue was dissolved in ethyl acetate
13. 13
    Extraktionextracted with 1N HCl (3×)
14. 14
    Extraktionextracted with ethyl acetate (2×)
15. 15
    TrocknenThe organic layer was dried (MgSO4)
16. 16
    Einengenconcentrated
17. 17
    Sonstigepurified by flash column chromatography (silica gel, 0 to 10% isopropanol/hexanes)

Vorschrift

To a mixture of 4-Bromo-benzene-1,2-diamine (5.0 g), Boc-L-proline (6.0 g), and 4-methylmorpholine (5.88 mL) in DMF (100 mL) was added HATU (10.7 g). Reaction mixture was stirred for 16 hours and then concentrated. Residue was dissolved in ethyl acetate and washed with 5% lithium chloride solution (2×), brine and dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 30 to 60% ethyl acetate/hexanes) to a dark brown foam. Brown foam was dissolved in ethanol (100 mL) and heated in a sealed tube at 110-130° C. for 2 days. Reaction mixture was cooled and concentrated. Residue was dissolved in ethyl acetate and extracted with 1N HCl (3×). Aqueous layer was basified with 50% NaOH solution to pH 10 and extracted with ethyl acetate (2×). The organic layer was dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 0 to 10% isopropanol/hexanes) to give 2-(6-Bromo-1H-benzoimidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (6.5 g) as an off-white foam: LCMS-ESI+: calc'd for C16H21BrN3O2: 367.26 (M+H+). Found: 365.8, 367.8 (M+H+).

Quelle