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

HRID 542649ノート

反応式

HRID 542649 の反応式
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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-20 °C

実験手順

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.

後処理

  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.)

出典と根拠

ORDレコード
ord-f3fcd17253b247d4802b64f64dfc7d3c
出典データセット
uspto-grants-1987_04
特許番号
US04658013

反応ノート

読み込み中…