Z-Tyr(Bzl)-OH → (N-benzyloxycarbonyl-O-benzyl-L-tyrosyl)-N-methyl-D-alanine methyl ester

HRID 484925Notes

Reaction equation

HRID 484925 reaction equation
C(N(C(C)C)CC)(C)C.C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[CH2:25]([O:32][C:33]([NH:35][C@H:36]([C:52](O)=[O:53])[CH2:37][C:38]1[CH:43]=[CH:42][C:41]([O:44][CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)=[CH:40][CH:39]=1)=[O:34])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.Br.[CH3:56][O:57][C:58](=[O:63])[C@@H:59]([CH3:62])[NH:60][CH3:61]>O1CCCC1>[CH3:56][O:57][C:58](=[O:63])[C@@H:59]([CH3:62])[N:60]([C:52](=[O:53])[C@H:36]([CH2:37][C:38]1[CH:39]=[CH:40][C:41]([O:44][CH2:45][C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=2)=[CH:42][CH:43]=1)[NH:35][C:33]([O:32][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:34])[CH3:61]

Participants

6

Reactant 4

HCID 47600Z-Tyr(Bzl)-OHHCID 73910Diphenylphosphinic chlorideHCID 81531Diisopropylethylamine2×HCID 86740225N-methyl-D-alanine methyl ester hydrobromide

Product 1

HCID 54142792(N-benzyloxycarbonyl-O-benzyl-L-tyrosyl)-N-methyl-D-alanine methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

Diisopropylethylamine (1.29 g.), then diphenylphosphinic chloride (2.37 g.), were added to a solution of N-benzyloxycarbonyl-O-benzyl-L-tyrosine (4.05 g.) in tetrahydrofuran (30 ml.) maintained at -20° C., and the mixture was stirred at that temperature for 10 minutes. A solution of N-methyl-D-alanine methyl ester hydrobromide (1.98 g.) in tetrahydrofuran (20 ml.) was then added, followed by diisopropylethylamine (1.29 g.). The mixture was stirred for two hours at 0° C., then overnight at room temperature, then filtered, stripped of volatiles and distributed between ethyl acetate and aqueous citric acid (5%). The ethyl acetate layer was washed with water, saturated aqueous sodium bicarbonate, water again and saturated aqueous sodium chloride, then dried over magnesium sulfate and concentrated to a yellow gum (about 6 g.). Purification of the yellow gum by high pressure liquid chromatography on silica gel (350 g.) using hexane-ethyl acetate (7:3) as the eluant afforded (N-benzyloxycarbonyl-O-benzyl-L-tyrosyl)-N-methyl-D-alanine methyl ester as a clear gum (3.2 g.) containing about a one-sixth molar amount of ethyl acetate as shown by NMR spectral analysis.

Workup

  1. stirringThe mixture was stirred for two hours at 0° C.
  2. filtrationovernight at room temperature, then filtered
  3. washThe ethyl acetate layer was washed with water, saturated aqueous sodium bicarbonate, water again
  4. dry with materialsaturated aqueous sodium chloride, then dried over magnesium sulfate
  5. concentrationconcentrated to a yellow gum (about 6 g.)
  6. customPurification of the yellow gum by high pressure liquid chromatography on silica gel (350 g.)

Sources & evidence

ORD record
ord-46fbc2984b914043ba6d31869a3a2f89
Source dataset
uspto-grants-1985_08
Patent number
US04533655

Reaction notes

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