反应详情

温度

5 °C

A stirred solution of 4-[(methylsulfonyl)amino]-γ-oxobenzenebutanoic acid as prepared in Preparation 2 (12.0 g, 0.044 mol) in DMF (100 ml) under N2 is cooled in an ice bath to 5° C. and treated with 1-hydroxybenzotriazole (5.94 g, 0.044 mol) and N,N'-dicyclohexylcarbodiimide (9.08 g, 0.044 mol). After 1 hour, ethylheptylamine (6.3 g, 0.044 mol) is added; after an additional 30 minutes the ice bath is removed and the mixture is kept at ambient temperature for 18 hours. The reaction mixture is filtered over a Celite filter aid and the filtrate is concentrated under vacuum. The resulting material is dissolved in CH2Cl2 ; washed with dilute HCl, NaHCO3 and brine; dried (Na2SO4) and concentrated. The residue is chromatographed over silica gel (1.25 kg) with 5% MeOH:1% NH4OH:CH2Cl2. The N-ethyl-N-heptyl-γ-oxo-4-[(methylsulfonyl)amino]benzenebutanamide thus obtained is crystallized from EtOAc:SSB to yield 10.77 g, mp 100°-102° C. and 2.32 g, mp 99°-101° C. The analytical sample has a mp 102°-103° C.

1. customafter an additional 30 minutes the ice bath is removed
2. waitthe mixture is kept at ambient temperature for 18 hours
3. filtrationThe reaction mixture is filtered over a Celite
4. filtrationfilter aid
5. concentrationthe filtrate is concentrated under vacuum
6. dissolutionThe resulting material is dissolved in CH2Cl2
7. washwashed with dilute HCl, NaHCO3 and brine
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated
10. customThe residue is chromatographed over silica gel (1.25 kg) with 5% MeOH