反応 #159540

反応方程式

N-bromosuccinimide

sodium bis(trimethylsilyl)amide

THF

isothiocyanate

hydrochloric acid

(1-hydroxycyclobutyl)methanesulfonamide

→

product

(S)-3-(8,8-Dioxo-5-oxa-8lambda6-thia-7-azaspiro[3.5]non-6-en-6-ylamino)-3-phenylpropan-1-ol

溶媒

acetonitrile

methanol

water

dioxane

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 at constant temperature for 30 minutes
4. 4
   抽出extracted twice with 20 ml of ethyl acetate
5. 5
   洗浄The combined organic phases were washed with 20 ml of saturated aqueous ammonium chloride solution
6. 6
   乾燥dried over MgSO4
7. 7
   濃縮concentrated by rotary evaporation
8. 8
   workup.DISSOLUTIONThe residue was dissolved in 3 ml of methanol
9. 9
   workup.ADDITION0.30 ml of concentrated hydrochloric acid was added
10. 10
    workup.STIRRINGthe mixture was stirred for 1.5 hours
11. 11
    乾燥the organic phase was dried over MgSO4
12. 12
    濃縮concentrated by rotary evaporation
13. 13
    その他the residue was purified in a purification laboratory by means of preparative HPLC
14. 14
    その他had formed as part of the products
15. 15
    workup.STIRRINGthe mixture was stirred at room temperature for 6 hours
16. 16
    濃縮concentrated by rotary evaporation
17. 17
    workup.DISSOLUTIONthe residue was dissolved in a little acetonitrile, water
18. 18
    workup.ADDITIONwas added

実験手順

Under inert gas, 192 mg of (1-hydroxycyclobutyl)methanesulfonamide were dissolved in 1.5 ml of NMP, and admixed at −10° C. with 0.58 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 30 minutes, 207 mg of N-bromosuccinimide were added in 4 portions and the resulting reaction solution was stirred at constant temperature for 30 minutes. The reaction mixture was diluted with 50 ml of water and extracted twice with 20 ml of ethyl acetate. The combined organic phases were washed with 20 ml of saturated aqueous ammonium chloride solution, dried over MgSO4 and concentrated by rotary evaporation. The residue was dissolved in 3 ml of methanol, 0.30 ml of concentrated hydrochloric acid was added and the mixture was stirred for 1.5 hours. The reaction solution was admixed with 15 ml of water and ethyl acetate, the organic phase was dried over MgSO4 and concentrated by rotary evaporation, and the residue was purified in a purification laboratory by means of preparative HPLC. The product-containing fractions were combined and freed of the solvent under reduced pressure, and the aqueous residue was lyophilized. To cleave the ethyl trifluoroacetate which had formed as part of the products, the lyophilizate was dissolved again in methanol, 0.5 ml of a 4 N solution of hydrochloric acid in dioxane was added and the mixture was stirred at room temperature for 6 hours. The solution was admixed with 10 ml of acetonitrile and concentrated by rotary evaporation, and the residue was dissolved in a little acetonitrile, water was added and the mixture was lyophilized. This gave the product (187.4 mg) with a molecular weight of 324.4 g/mol (C15H20N2O4S); MS (ESD: m/e=325 (M+H+).

出典