Sodium Carbonate → (S)-chloromethyl 2-((tert-butoxycarbonyl)amino)propanoate

HRID 920881Notes

Reaction equation

HRID 920881 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH3:13])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].S(Cl)(O[CH2:24][Cl:25])(=O)=O>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl.O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH3:13])[C:10]([O:12][CH2:24][Cl:25])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 85082Tert-butoxycarbonylalanineHCID 2733556Chloromethyl chlorosulfate

Product 1

HCID 11481803(S)-chloromethyl 2-((tert-butoxycarbonyl)amino)propanoate

Reagents, catalysts & solvents 3

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a vigorously stirred mixture of (S)-2-((tert-butoxycarbonyl)amino)propanoic acid (1 g, 5.29 mmol), tetrabutylammonium hydrogen sulfate (0.359 g, 1.057 mmol), and Na2CO3 (2.80 g, 26.4 mmol) in DCM 20 (mL) and water (20 mL) cooled in an ice/water bath was slowly added chloromethyl chlorosulfate (1.09 mL, 10.57 mmol) over a 4 min period. After stirring in ice/water bath for 30 min the cold bath was removed and the reaction allowed to stir at room temperature. After stirring 16 h at room temperature the reaction was diluted with water and extracted with DCM. The aqueous layer was back extracted with DCM and the combined organic layers were dried over MgSO4, filtered and concentrated to afford Preparation 5A (1.64 g).

Workup

  1. temperaturecooled in an ice/water bath
  2. customover a 4 min
  3. customwas removed
  4. stirringAfter stirring 16 h at room temperature the reaction
  5. additionwas diluted with water
  6. extractionextracted with DCM
  7. extractionThe aqueous layer was back extracted with DCM
  8. dry with materialthe combined organic layers were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford

Sources & evidence

ORD record
ord-3ef57154ebf9481f9975ca3c8df3dad9
Source dataset
uspto-grants-2016_03
Patent number
US09273075B2

Reaction notes

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