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

HRID 542649Notes

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

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 hexaneethyl 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

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

Sources & evidence

ORD record: ord-f3fcd17253b247d4802b64f64dfc7d3c
Source dataset: uspto-grants-1987_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04658013

Reaction notes

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