Acetamide → HCID 19348680, compound

Temperature

40 °C

0.63 g of N,N'-carbonyldiimidazole was added to a solution of 1.208 g of N-(2-t-butyl-5-carboxyphenyl)-3-(2,4-dimethoxyphenyl)nonanamide (prepared as described in Preparation 31D) in 12 ml of tetrahydrofuran, and the resulting mixture was stirred at 40° C. for 3 hours. At the end of this time, the reaction mixture was poured into a mixture of a saturated aqueous solution of sodium hydrogencarbonate and ethyl acetate and was partitioned between the aqueous and organic phases. The ethyl acetate phase was washed three times with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the resulting residue was dissolved in 10 ml of dimethylacetamide to produce a solution containing an active ester compound. Meanwhile, 0.61 g of potassium t-butoxide was added to a solution of 0.304 g of acetamide in 10 ml of dimethylacetamide, and the resulting mixture was stirred for 30 minutes. The solution containing an active ester compound prepared above was added dropwise to the mixture thus obtained, and the resulting mixture was stirred for 1 hour. At the end of this time, the reaction mixture was poured into a saturated aqueous solution of potassium hydrogensulfate and the aqueous mixture was extracted three times with ethyl acetate. The combined extracts were washed three times with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, after which the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel using a 1:1 by volume mixture of hexane and ethyl acetate as the eluent. The desired fractions were collected and concentrated by evaporation under reduced pressure. The concentrate was triturated with hexane to cause crystallization, giving 0.985 g of the title compound.

1. customwas partitioned between the aqueous and organic phases
2. washThe ethyl acetate phase was washed three times with a saturated aqueous solution of sodium chloride
3. dry with materialdried over anhydrous sodium sulfate
4. customThe solvent was removed by distillation under reduced pressure
5. dissolutionthe resulting residue was dissolved in 10 ml of dimethylacetamide
6. customto produce a solution
7. stirringthe resulting mixture was stirred for 30 minutes
8. customprepared
9. additionabove was added dropwise to the mixture
10. customthus obtained
11. stirringthe resulting mixture was stirred for 1 hour
12. extractionthe aqueous mixture was extracted three times with ethyl acetate
13. washThe combined extracts were washed three times with a saturated aqueous solution of sodium chloride
14. dry with materialdried over anhydrous sodium sulfate
15. customafter which the solvent was removed by distillation under reduced pressure
16. customThe resulting residue was purified by column chromatography through silica gel using a 1:1
17. additionby volume mixture of hexane and ethyl acetate as the eluent
18. customThe desired fractions were collected
19. concentrationconcentrated by evaporation under reduced pressure
20. customThe concentrate was triturated with hexane
21. customcrystallization

ORD record

ord-88c57e0542614bd188b4813f16806258

Source dataset

uspto-grants-1999_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05880147