反应详情

A mixture of Intermediate 7 (250 mg, 0,83 mmol) and 3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)benzoic acid (196 mg, 0.83 mmol, e.g. available from Fluka) in N,N-dimethylformamide (4 ml) was treated with N,N-diisopropylethylamine (0.569 ml, 3.3 mmol) and (1H-1,2,3-benzotriazol-1-yloxy)(tri-1-pyrrolidinyl)phosphonium hexafluorophosphate (472 mg, 0.91 mmol) and allowed to stir at room temperature for 4 hours. An additional portion of (1H-1,2,3-benzotriazol-1-yloxy)(tri-1-pyrrolidinyl)phosphonium hexafluorophosphate (0.5 equivalents, 0.41 mmol) was added and the mixture stirred for an additional hour. The solvent was evaporated and the residue partitioned between ethyl acetate (50 ml) and aqueous sodium bicarbonate solution (50 ml); saturated sodium chloride solution was added and the layers allowed to separate overnight. The aqueous layer was further extracted with ethyl acetate (50 ml), and the organic fractions collected, dried (Na2SO4) and evaporated; however the residue contained very little product. A white solid was filtered off from the aqueous layer and dried to give the title compound (193 mg). LCMS showed MH+=523; TRET=2.99 min.

1. stirringthe mixture stirred for an additional hour
2. customThe solvent was evaporated
3. customthe residue partitioned between ethyl acetate (50 ml) and aqueous sodium bicarbonate solution (50 ml)
4. additionsaturated sodium chloride solution was added
5. customto separate overnight
6. extractionThe aqueous layer was further extracted with ethyl acetate (50 ml)
7. customthe organic fractions collected
8. dry with materialdried (Na2SO4)
9. customevaporated
10. filtrationA white solid was filtered off from the aqueous layer
11. customdried