反応 #159535

反応方程式

isothiocyanate

sodium bis(trimethylsilyl)amide

THF

N-bromosuccinimide

1-(1-hydroxy-1-methyl-ethyl)cyclopropanesulfonamide

→

product

(S)-3-(8,8-Dimethyl-4,4-dioxo-7-oxa-4lambda6-thia-5-azaspiro[2.5]oct-5-en-6-ylamino)-3-phenylpropan-1-ol

溶媒

water

NMP

反応条件

後処理

1. 1
   その他prepared above
2. 2
   その他the resulting reaction solution
3. 3
   workup.STIRRINGwas stirred again for 10 minutes
4. 4
   抽出extracted three times with 20 ml of ethyl acetate
5. 5
   洗浄The combined organic phases were washed with saturated aqueous sodium chloride solution
6. 6
   乾燥dried over Na2SO4
7. 7
   濃縮concentrated by rotary evaporation
8. 8
   workup.DISSOLUTIONThe residue was dissolved in 5 ml of methanol
9. 9
   workup.ADDITION0.20 ml of concentrated hydrochloric acid was added
10. 10
    workup.STIRRINGthe mixture was stirred for 1.5 hours
11. 11
    workup.ADDITIONAfter the addition of 1.26 ml of 1 N aqueous sodium hydroxide solution
12. 12
    濃縮the mixture was concentrated by rotary evaporation
13. 13
    その他purified in a purification laboratory by means of preparative HPLC

実験手順

250 mg of 1-(1-hydroxy-1-methyl-ethyl)cyclopropanesulfonamide were dissolved in 2 ml of NMP, and admixed while cooling with ice with 0.70 ml of a 2 N solution of sodium bis(trimethylsilyl)amide in THF and, after stirring for 5 minutes, with the isothiocyanate solution prepared above. After stirring for 1.5 hours, 248 mg of N-bromosuccinimide were added and the resulting reaction solution was stirred again for 10 minutes. The reaction mixture was added to 20 ml of water and extracted three times with 20 ml of ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over Na2SO4 and concentrated by rotary evaporation. The residue was dissolved in 5 ml of methanol, 0.20 ml of concentrated hydrochloric acid was added and the mixture was stirred for 1.5 hours. After the addition of 1.26 ml of 1 N aqueous sodium hydroxide solution, the mixture was concentrated by rotary evaporation and purified in a purification laboratory by means of preparative HPLC. After lyophilization of the product-containing fractions, the product (26 mg) was thus obtained with a molecular weight of 338.4 g/mol (C16H22N2O4S); MS (ESI): m/e=339 (M+H+).

出典