Triethylamine → (N-benzyloxycarbonyl-O-benzyl-L-tyrosyl)-D-alanine methyl ester

HRID 484769Notes

Reaction equation

HRID 484769 reaction equation
C(N(CC)CC)C.C(OC(Cl)=O)C(C)C.[CH2:16]([O:23][C:24]([NH:26][C@H:27]([C:43](O)=[O:44])[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[CH:31][CH:30]=1)=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.Cl.[CH3:47][O:48][C:49](=[O:53])[C@@H:50]([CH3:52])[NH2:51]>CC(C)=O.C(Cl)(Cl)Cl>[CH3:47][O:48][C:49](=[O:53])[C@@H:50]([CH3:52])[NH:51][C:43](=[O:44])[C@H:27]([CH2:28][C:29]1[CH:30]=[CH:31][C:32]([O:35][CH2:36][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)=[CH:33][CH:34]=1)[NH:26][C:24]([O:23][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:25]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 47600Z-Tyr(Bzl)-OHHCID 62365Isobutyl chloroformateHCID 11182647Methyl D-alaninate hydrochloride

Product 1

HCID 13850973(N-benzyloxycarbonyl-O-benzyl-L-tyrosyl)-D-alanine methyl esterYield 75.7%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6212ChloroformSolvent

Conditions

Temperature
-20 °C

Procedure

Triethylamine (5.7 ml.), then isobutylchloroformate (5.3 ml.), were added with stirring to a solution of N-benzyloxycarbonyl-O-benzyl-L-tyrosine (16.68 g.) in acetone (175 ml.) maintained at -20° C. The solution was stirred for 10 minutes at -20° C., then D-alanine methyl ester hydrochloride (6.4 g.) and triethylamine (5.7 ml.) in chloroform (65 ml.) were added. Stirring was continued one hour at this temperature, then four hours at room temperature. The mixture was filtered and the filtrate was stripped of volatiles. The residue and the filtration solid were combined and distributed between water (200 ml.) and ethyl acetate (250 ml.). Part of the product was collected by filtration and washed with aqueous hydrochloric acid, water, saturated sodium bicarbonate and water. The ethyl acetate layer was washed with cold aqueous hydrochloric acid (0.5N), water, saturated aqueous sodium bicarbonate, water again and saturated aqueous sodium chloride and stripped of volatiles, yielding another part of the product. The two parts were combined and recrystallized from absolute ethanol, affording (N-benzyloxycarbonyl-O-benzyl-L-tyrosyl)-D-alanine methyl ester (15.28 g.; m.r. 161°-163° C.; [α]D25 -11.7°, c=2, dimethylformamide)

Workup

  1. stirringStirring
  2. waitwas continued one hour at this temperature
  3. customfour hours
  4. customat room temperature
  5. filtrationThe mixture was filtered
  6. filtrationThe residue and the filtration solid
  7. filtrationPart of the product was collected by filtration
  8. washwashed with aqueous hydrochloric acid, water, saturated sodium bicarbonate and water
  9. washThe ethyl acetate layer was washed with cold aqueous hydrochloric acid (0.5N), water, saturated aqueous sodium bicarbonate, water again
  10. customyielding another part of the product
  11. customrecrystallized from absolute ethanol

Sources & evidence

ORD record
ord-4f707fb36f7143dca4e75a659067e370
Source dataset
uspto-grants-1985_08
Patent number
US04533657

Reaction notes

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