1,4-Dioxane → S-(acetamidomethyl)-N-(tert-butoxycarbonyl)-L-cysteine

HRID 259472Notes

Reaction equation

HRID 259472 reaction equation
Cl.[C:2]([NH:5][CH2:6][S:7][CH2:8][C@@H:9]([C:11]([OH:13])=[O:12])[NH2:10])(=[O:4])[CH3:3].O1CCOCC1.[O-2].[Mg+2].[C:22]([O:26][C:27](N=[N+]=[N-])=[O:28])([CH3:25])([CH3:24])[CH3:23]>C(OCC)(=O)C.C1C=CC=CC=1.O>[C:22]([O:26][C:27]([NH:10][C@H:9]([C:11]([OH:13])=[O:12])[CH2:8][S:7][CH2:6][NH:5][C:2](=[O:4])[CH3:3])=[O:28])([CH3:25])([CH3:24])[CH3:23]

Participants

8

Reactant 4

HCID 312751,4-DioxaneHCID 61256Carbonazidic acid, 1,1-dimethylethyl esterHCID 6850729Magnesium monoxideHCID 1621100228798-28-9

Product 1

HCID 88223S-(acetamidomethyl)-N-(tert-butoxycarbonyl)-L-cysteine

Reagents, catalysts & solvents 3

HCID 241BenzeneSolvent2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

22.8 grams (0.1 mole) of S-acetamidomethylcysteine hydrochloride are dissolved in 250 ml. of 50% dioxane (peroxide-free) in a 500 ml. 3-neck flask equipped with a mechanical stirrer and condenser. 12 grams of magnesium oxide (0.3 mole) are added, and the mixture is stirred at room temperature for 30 minutes. 15.7 grams (0.11 mole) of redistilled t-butoxycarbonylazide are added, and the mixture is stirred for 20 hours in an oil bath at 45° C. The reaction mixture is then cooled to room temperature, and 1 liter of water is added. The aqueous mixture is washed with 2 × 250 ml. of ethyl acetate, cooled in an ice bath, and acidified to pH 3 with 50% citric acid. The acidic solution is then saturated with sodium chloride and extracted with ethyl acetate. The extracts are washed twice with 200 ml. of saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and evaporated in vacuo to yield an amorphous solid. The solid is dissolved in warm ethyl acetate, and 2 volumes of benzene are added. Upon standing at room temperature, the product crystallizes and, after filtration, is washed with benzene and dried in vacuo. A second and third crop are obtained by adding benzene to the filtrates and seeding. After drying in vacuo, 11 grams of N-t-butoxycarbonyl-S-acetamido-methylcysteine, m.p. 110° - 112° C., are obtained.

Workup

  1. custom3-neck flask equipped with a mechanical stirrer and condenser
  2. stirringthe mixture is stirred for 20 hours in an oil bath at 45° C
  3. temperatureThe reaction mixture is then cooled to room temperature
  4. washThe aqueous mixture is washed with 2 × 250 ml
  5. temperatureof ethyl acetate, cooled in an ice bath
  6. extractionsaturated with sodium chloride and extracted with ethyl acetate
  7. washThe extracts are washed twice with 200 ml
  8. dry with materialof saturated sodium chloride solution, dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customto yield an amorphous solid
  12. customUpon standing at room temperature
  13. customthe product crystallizes
  14. filtrationafter filtration
  15. washis washed with benzene
  16. customdried in vacuo
  17. customA second and third crop are obtained
  18. dry with materialAfter drying in vacuo, 11 grams of N-t-butoxycarbonyl-S-acetamido-methylcysteine, m.p. 110° - 112° C.
  19. customare obtained

Sources & evidence

ORD record
ord-31ceb9ec231148dc96fd0dbbebfc5c4c
Source dataset
uspto-grants-1977_07
Patent number
US04038306

Reaction notes

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