Methyl iodide → HCID 178489710, compound

HRID 339862Notes

Reaction equation

HRID 339862 reaction equation
[Si]([O:8][CH2:9][CH2:10][C@H:11]([NH:18][C:19]1[O:20][C:21]([CH3:35])([CH3:34])[CH:22]([C:27]2[CH:28]=[C:29]([OH:33])[CH:30]=[CH:31][CH:32]=2)[S:23](=[O:26])(=[O:25])[N:24]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)(C(C)(C)C)(C)C.CI.[CH3:38][Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1.O.S([O-])([O-])(=O)=S.[Na+].[Na+]>[CH3:38][O:33][C:29]1[CH:28]=[C:27]([CH:22]2[C:21]([CH3:34])([CH3:35])[O:20][C:19]([NH:18][C@H:11]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:10][CH2:9][OH:8])=[N:24][S:23]2(=[O:26])=[O:25])[CH:32]=[CH:31][CH:30]=1

Participants

7

Reactant 3

HCID 6328Methyl iodide2×HCID 2724254Sodium bis(trimethylsilyl)amide2×HCID 178431689HCID 178431689, compound

Product 1

HCID 178489710HCID 178489710, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 24477Sodium ThiosulfateSolvent

Procedure

To a solution of 452 mg of 3-{2-[(S)-3-(tert-butyldimethylsilanyloxy)-1-phenylpropylamino]-6,6-dimethyl-4,4-dioxo-5,6-dihydro-4H-4lambda6-1,4,3-oxathiazin-5-yl}phenol and 148 mg of methyl iodide in THF at 0° C. was added dropwise 0.44 ml of a 2 N solution of sodium bis(trimethylsilyl)amide in THF. After stirring at constant temperature for 45 minutes and then warming up to room temperature, the reaction solution was stirred for a further 4 hours and then the conversion was checked by LCMS. A further 0.20 ml of the 2 N solution of sodium bis(trimethylsilyl)amide in THF and 114 mg of methyl iodide were added. After stirring at room temperature for 16 hours, the reaction solution was diluted with 60 ml of water, 5 ml of 5% aqueous sodium thiosulfate solution were added and the mixture was extracted twice with 30 ml of ethyl acetate. The combined organic phases were dried over MgSO4 and concentrated by rotary evaporation. To detach the protecting group, the residue was dissolved in 5 ml of methanol and, after addition of 0.5 ml of concentrated hydrochloric acid, stirred at room temperature for 1 hour. The reaction solution was diluted with 50 ml of water and extracted twice with ethyl acetate. The combined organic phases were 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 lyophilized. This gave the product (41.1 mg) with a molecular weight of 418.5 g/mol (C21H26N2O5S); MS (ESI): m/e=419 (M+H+).

Workup

  1. stirringthe reaction solution was stirred for a further 4 hours
  2. stirringAfter stirring at room temperature for 16 hours
  3. additionwere added
  4. extractionthe mixture was extracted twice with 30 ml of ethyl acetate
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. concentrationconcentrated by rotary evaporation
  7. dissolutionthe residue was dissolved in 5 ml of methanol
  8. additionafter addition of 0.5 ml of concentrated hydrochloric acid
  9. stirringstirred at room temperature for 1 hour
  10. additionThe reaction solution was diluted with 50 ml of water
  11. extractionextracted twice with ethyl acetate
  12. dry with materialThe combined organic phases were dried over MgSO4
  13. concentrationconcentrated by rotary evaporation
  14. customthe residue was purified in a purification laboratory by means of preparative HPLC

Sources & evidence

ORD record
ord-10193e35f40f49da98a5a6ce2cbf9ace
Source dataset
uspto-grants-2014_11
Patent number
US08895547B2

Reaction notes

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