反应详情

A mixture of 2-amino-5-[(S)-(+)-3-hydroxy-2-methylpropoxy]benzoic acid hydrochloride (200 mg, 0.76 mmol), 2-amino-N-isopropylacetamide*HCl (INTERMEDIATE I.1) (105 mg, 0.70 mmol) and triethylamine (0.23 mL, 1.68 mmol) in DMF (5 mL) was stirred at room temperature for 5 min. EDC (176 mg, 0.92 mmol) and HOBt (124 mg, 0.92 mmol) were added and stirring continued at room temperature for 16 h. The mixture was partitioned between ethyl acetate and sat. NaHCO3 (aq.) and the aqueous extracted with additional ethyl acetate. The combined organics were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The crude 2-amino-5-[(S)-(+)-3-hydroxy-2-methylpropoxy]-N-(isopropylcarbamoylmethyl)benzamide (INTERMEDIATE VIII.1) was used directly in the next reaction.

1. stirringstirring
2. waitcontinued at room temperature for 16 h
3. customThe mixture was partitioned between ethyl acetate and sat. NaHCO3 (aq.)
4. extractionthe aqueous extracted with additional ethyl acetate
5. washThe combined organics were washed with brine
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude 2-amino-5-[(S)-(+)-3-hydroxy-2-methylpropoxy]-N-(isopropylcarbamoylmethyl)benzamide (INTERMEDIATE VIII.1) was used directly in the next reaction