Water → HCID 11099982, compound

HRID 2243829Notes

Reaction equation

HRID 2243829 reaction equation
[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8]C(O)=CC=1.[OH-].[K+].S(OC)(O[CH3:30])(=O)=O.O.[CH2:34]1[CH2:38][O:37][CH2:36][CH2:35]1>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.CCOCC>[CH2:17]([O:16][C:14]([N:1]([CH3:30])[C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:35]=[CH:34][C:38]([O:37][CH3:36])=[CH:8][CH:9]=1)=[O:15])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

8

Reactant 5

HCID 962WaterHCID 6497Dimethyl SulfateHCID 8028TetrahydrofuranHCID 14797Potassium HydroxideHCID 712438N-benzyloxycarbonyl-l-tyrosine

Product 1

HCID 11099982HCID 11099982, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 3283Diethyl EtherSolvent

Procedure

To a stirred solution of Z-Tyr-OH (63.24 g, 200 mmol) in THF (900 ml) at 0° C. was added finely powdered KOH (112.72 g, 2 mol) in portions, followed by the addition of tetrabutylammonium hydrogen sulfate (6.36 g, 10% by weight). Then, dimethyl sulfate (127.2 ml, 1.33 mol) was added dropwise over 30 min, while maintaining the reaction mixture below 4° C. The reaction was stirred for an additional 30 min and H2O (950 ml) was added. After stirring 5 h at 0° C., the reaction was diluted with ether (1500 ml), the aqueous layer was separated, and the organic layer was extracted with aq NaHCO3 (2×500 ml, sat). The combined aqueous layers were acidified to pH 1 with aq 1M KHSO4, and extracted with EtOAc (5×500 ml). The organic layers were combined, dried (Na2SO4), filtered and concentrated. The residue was precipitated with ethyl ether and filtered to give E1 as a white solid (53.85 g, 78%).

Workup

  1. temperaturewhile maintaining the reaction mixture below 4° C
  2. stirringAfter stirring 5 h at 0° C.
  3. customthe aqueous layer was separated
  4. extractionthe organic layer was extracted with aq NaHCO3 (2×500 ml, sat)
  5. extractionextracted with EtOAc (5×500 ml)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was precipitated with ethyl ether
  10. filtrationfiltered

Sources & evidence

ORD record
ord-f8c5bef645bb446bba5021e86d1e71fb
Source dataset
uspto-grants-2010_03
Patent number
US07678765B2

Reaction notes

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