L-Serine → Z-Glu(OBzl)-Ser-OH

HRID 462928Notes

Reaction equation

HRID 462928 reaction equation
[NH:1]([C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[C@H:2]([C:15]([OH:17])=O)[CH2:3][CH2:4][C:5](=[O:14])[O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.ON1C(=O)CCC1=O.[NH2:36][C@H:37]([C:40]([OH:42])=[O:41])[CH2:38][OH:39].C(N(CC)CC)C>O1CCCC1.CN1CCOCC1.ClC(OCC(C)C)=O.O>[NH:1]([C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[C@H:2]([C:15]([NH:36][C@H:37]([C:40]([OH:42])=[O:41])[CH2:38][OH:39])=[O:17])[CH2:3][CH2:4][C:5](=[O:14])[O:6][CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

9

Reactant 4

HCID 5951L-SerineHCID 8471TriethylamineHCID 80170N-HydroxysuccinimideHCID 30498605-(Phenylmethyl) hydrogen N-((phenylmethoxy)carbonyl)-L-glutamate

Product 1

HCID 13385129Z-Glu(OBzl)-Ser-OHYield 76.9%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 79724-MethylmorpholineSolventHCID 8028TetrahydrofuranSolvent2×HCID 62365Isobutyl chloroformateSolvent

Conditions

Temperature
-15 °C

Procedure

To a solution of Z-Glu(OBzl)OH (5.62 g, 15 m mole) (Hayakawa et al. Bull. Chem. Soc. Japan, 39: 391 (1966)) in tetrahydrofuran (20 ml), N-methylmorpholin (1.53 ml) and isobutyl chloroformate (1.98 ml) were added with stirring at -15° C. To this mixture a solution of HOSu (N-hydroxy-succinimide) (3.45 g) in tetrahydrofuran (10 ml) was added with stirring at -15° C. The mixture was stirred at -15° C. for 30 min., and at 0° C. for 30 min. To this mixture a solution of H-Ser-OH (3.15 g, 30 mmole) in H2O (15 ml) containing triethylamine (4.2 ml) was added with stirring at 0° C. The mixture was stirred at 0° C. for 2 hr. and at room temperature for 15 hr. After removal of the organic solvent, the residue was extracted with three portions of ethyl acetate, which were washed successively with 1N citric acid and sat. NaCl solution, and dried over Na2SO4. After evaporating the residue was solidified by addition of ether. Reprecipitation from methanol-ether to yield (I) (5.29 g, 76.9%), RfI 0.74 RfII 0.70, mp 104°-105° C. [α]D27 +5.7 (C=1.12 in methanol).

Workup

  1. stirringwith stirring at -15° C
  2. stirringThe mixture was stirred at -15° C. for 30 min.
  3. additionwas added
  4. stirringwith stirring at 0° C
  5. stirringThe mixture was stirred at 0° C. for 2 hr
  6. waitand at room temperature for 15 hr
  7. customAfter removal of the organic solvent
  8. extractionthe residue was extracted with three portions of ethyl acetate, which
  9. washwere washed successively with 1N citric acid and sat. NaCl solution
  10. dry with materialdried over Na2SO4
  11. customAfter evaporating the residue
  12. additionwas solidified by addition of ether
  13. customReprecipitation from methanol-ether

Sources & evidence

ORD record
ord-759ebb41ab394f4cb105107fb97fa18c
Source dataset
uspto-grants-1985_05
Patent number
US04518527

Reaction notes

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