A solution of acid 1 and NMM,(0.54 mL, 4.92 mmol) in DMF (10 mL) was treated at room temperature with isobutyl chloroformate (0.64 mL, 4.92 mmol). After 30 min, pentylamine (0.57 mL, 4.92 mmol)was added. The reaction mixture wasstirred for 12 h.
The solvent was evaporated, and the residue was partitioned between ethyl acetate (25 mL) and water (25mL). The ethyl acetate layer was washed with 5% NaHCO3 (10 mL) and brine (20 mL), dried over Na2SO4, and evaporated. The residue was chromatographed on silica gel eluting with hexane and ethyl acetate (2:1) to give 0.33 g (33%) of tert-butoxycarbonylatedamino amide (2)
To acid 5 (4.0 g, 14.1 mmol) in CH2Cl2(70 mL) at 23℃ was added 1, 1’-carbonyldiimidazole (3.65 g, 22.5 mmol) in equal portions over 15 min. After the final addition, stirring was continued for 10 min, then N,O-dimethylhydroxylamine • HCl(3.43 g, 35.16 mmol)was added in one portion. The reaction was allowed to stir at 23℃ for 3 h.
Et2O was added (50 mL) and the reaction mixture was filtered. The filtrate was evaporated, diluted with Et2O(125 mL), washed with 5% aq. citric acid (2 x 50 mL) and brine (50 mL), and dried over MgSO4. The crude product was purified by flash chromatography (3:1 hexanes: EtOAc) to afford Weinreb amide 6 (4.29 g,93% yield) as a colorless oil.
A mixture of the benzoicacid (10 mmol), 4-methylbenzene-1-sulfonyl chloride (10 mmol), K2CO3(5.52 g, 40 mmol) and TEBAC (0.23 g, 1mmol) in 60 mL of benzene is stirred at reflux for 40 min.
To a stirred solution of N-protected amino acid 9(10 mmol), pyridine (0.5 ml) and Boc2O (3 g, 13 mmol) in an appropriate solvent (such asdioxane, DMF and CH3CN, 10-15 ml), ammonium hydrogencarbonate (1 g, 12.6 mmol) was added and the mixture was stirred for 4-16 h.
